147 results on '"Kenneth J. Sufka"'
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2. Evaluation of Glutamate Receptors for Anxiolytic And/Or Antidepressant Effects in an Avian Model of Treatment-Resistant Depression
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Stephen W. White, Gwendolyn D. SQUIRES, Sequioa J. SMITH, Gwendolyn M. WRIGHT, Kenneth J. SUFKA, John M. RIMOLDI, and Rama S. GADEPELLI
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- 2023
3. The kappa-opioid receptor agonist, triazole 1.1, reduces oxycodone self-administration and enhances oxycodone-induced thermal antinociception in male rats
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Hayley M. Schrock, Thomas E. Prisinzano, Kevin B. Freeman, Kenneth J. Sufka, Bruce E. Blough, C. Austin Zamarripa, and Tanya Pareek
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Male ,Nociception ,Agonist ,medicine.drug_class ,Receptors, Opioid, mu ,Triazole ,Self Administration ,Pharmacology ,κ-opioid receptor ,Article ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,medicine ,Animals ,Dose-Response Relationship, Drug ,business.industry ,Receptors, Opioid, kappa ,3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ,Antagonist ,Triazoles ,Rats ,Analgesics, Opioid ,chemistry ,business ,Self-administration ,Oxycodone ,Nalfurafine ,medicine.drug - Abstract
RATIONALE: Triazole 1.1 is a novel kappa-opioid receptor (KOR) agonist reported to produce antinociception without KOR-typical adverse effects. When combined with the mu-opioid receptor (MOR) agonist, oxycodone, triazole 1.1 blocks oxycodone-induced pruritis without producing sedation-like effects in nonhuman primates. However, it is unknown if triazole 1.1 can reduce the abuse-related effects or enhance the antinociceptive effects of oxycodone similarly to other KOR agonists. OBJECTIVES: The aim of the present study was to quantitatively compare the behavioral effects of triazole 1.1 to the KOR agonists, U50,488h and nalfurafine, on oxycodone self-administration and oxycodone-induced thermal antinociception when administered as mixtures with oxycodone. METHODS: In the self-administration study, male Sprague-Dawley (SD) rats (n=6) self-administered intravenous (i.v.) oxycodone alone (0.056 mg/kg/inj) or combined with U50,488h (0.032–0.32 mg/kg/inj), nalfurafine (0.00032–0.0032 mg/kg/inj), or triazole 1.1 (0.32–1.8 mg/kg/inj) under a progressive-ratio schedule of reinforcement. In a hot plate assay, male SD rats (n=6) received i.v. injections of oxycodone (1.0–5.6 mg/kg), U50,488h (1.0–18.0 mg/kg), nalfurafine (0.01–1.0 mg/kg), or triazole 1.1 (3.2–32.0 mg/kg) alone or in combinations of fixed proportion with oxycodone based on the relative potencies of the single drugs. Each study concluded with administration of the KOR antagonist nor-BNI and some degree of retesting of the previous conditions to verify that the behavioral effects were mediated by KOR activation. RESULTS: All KOR agonists reduced oxycodone self-administration in a dose-dependent manner. Moreover, all single drugs and drug combinations produced dose-dependent, fully efficacious thermal antinociception. All KOR agonist:oxycodone combinations produced either additive or super-additive thermal antinociception. Finally, each KOR agonist was blocked in effect by nor-BNI in both behavioral measures. CONCLUSION: This study demonstrates that triazole 1.1 reduces oxycodone’s reinforcing effects and enhances oxycodone-induced antinociception to degrees that are comparable to typical KOR agonists. Given triazole 1.1’s mild adverse-effect profile, developing MOR-KOR agonist combinations from the triazole 1.1 series may render new pain therapeutics with reduced abuse liability.
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- 2021
4. The conditioned place preference test for assessing welfare consequences and potential refinements in a mouse bladder cancer model.
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John V Roughan, Claire A Coulter, Paul A Flecknell, Huw D Thomas, and Kenneth J Sufka
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Medicine ,Science - Abstract
Most pre-clinical analgesic efficacy assays still involve nociceptive testing in rodents. This is despite concerns as to the relevance of these tests for evaluating the pain-preventative properties of drugs. More appropriate methods would target pain rather than nociception, but these are currently not available, so it remains unknown whether animal pain equates to the negatively affective and subjective/emotional state it causes in humans. Mouse cancer models are common despite the likelihood of substantial pain. We used Conditioned Place Preference (CPP) testing, assessments of thermal hyperalgesia and behaviour to determine the likelihood that MBT-2 bladder cancer impacts negatively on mouse welfare, such as by causing pain. There was no CPP to saline, but morphine preference in tumour bearing mice exceeded that seen in tumour-free controls. This occurred up to 10 days before the study end-point alongside reduced body weight, development of hyperalgesia and behaviour changes. These effects indicated mice experienced a negative welfare state caused by malaise (if not pain) before euthanasia. Due to the complexity of the assessments needed to demonstrate this, it is unlikely that this approach could be used for routine welfare assessment on a study-by-study basis. However, our results show mice in sufficiently similar studies are likely to benefit from more intensive severity assessment and re-evaluation of end-points with a view to implementing appropriate refinements. In this particular case, a refinement would have been to have euthanased mice at least 7 days earlier or possibly by provision of end-stage pain relief. CPP testing was found to be a helpful method to investigate the responses of mice to analgesics, possibly on a subjective level. These findings and those of other recent studies show it could be a valuable method of screening candidate analgesics for efficacy against cancer pain and possibly other pain or disease models.
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- 2014
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5. Effects of Cannabidiol and a Novel Cannabidiol Analog against Tactile Allodynia in a Murine Model of Cisplatin-Induced Neuropathy: Enhanced Effects of Sub-Analgesic Doses of Morphine
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Mahmoud A. ElSohly, Hannah M. Harris, Waseem Gul, and Kenneth J. Sufka
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Pharmacology ,Cisplatin ,business.industry ,Analgesic ,Tactile Allodynia ,Allodynia ,Complementary and alternative medicine ,Pharmacokinetics ,Murine model ,Preclinical Science and Clinical Studies - Research Article ,Morphine ,Medicine ,Pharmacology (medical) ,medicine.symptom ,business ,Cannabidiol ,medicine.drug - Abstract
Objective: This research examined whether a cannabidiol (CBD)-opioid pharmacotherapy could attenuate cisplatin-induced tactile allodynia. Methods: Mice (C57BL/6) were given 6 doses of 2.3 mg/kg cisplatin intraperitoneally (IP) on alternating days to induce tactile allodynia as quantified using an electric von Frey (eVF). Test groups in Experiment 1 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0 or 2.0 CBD, or the 2 drugs in combination. Test groups in Experiment 2 received either vehicle, 0.1 or 2.5 mg/kg morphine, 1.0, 2.0, 3.0, or 4.0 mg/kg NB2111 (a long-acting CBD analogue), or the 2 drugs in combination. Drugs were administered IP 45 min before eVF assessment. Results: Cisplatin produced tactile allodynia that was attenuated by 2.5 mg/kg morphine. Both CBD and NB2111 produced dose-dependent attenuation of tactile allodynia. CBD and NB2111, given in combination with sub-analgesic doses of morphine, produced attenuation of tactile allodynia equivalent to 2.5 mg/kg morphine. Conclusions: While both CBD and NB2111, either alone or in combination with sub-analgesic doses of opioids, exhibited analgesic effects, NB2111 could be capable of superior analgesia over time by virtue of enhanced pharmacokinetics.
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- 2018
6. Effects of Cannabidiol on Morphine Conditioned Place Preference in Mice
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Kenneth J. Sufka, Hannah M. Harris, Mahmoud A. ElSohly, Waseem Gul, and James Roland Markos
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Male ,Spatial Behavior ,Pharmaceutical Science ,Abuse deterrent ,Pharmacology ,Analytical Chemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Reward ,Drug Discovery ,medicine ,Animals ,Cannabidiol ,Addiction treatment ,Dose-Response Relationship, Drug ,Morphine ,biology ,business.industry ,Organic Chemistry ,biology.organism_classification ,Conditioned place preference ,030227 psychiatry ,Mice, Inbred C57BL ,Complementary and alternative medicine ,Opioid ,Conditioning, Operant ,Molecular Medicine ,Conditioning ,Cannabis ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
This study sought to determine whether the cannabis constituent cannabidiol attenuates the development of morphine reward in the conditioned place preference paradigm. Separate groups of mice received either saline or morphine in combination with one of four doses of cannabidiol using three sets of drug/no-drug conditioning trials. After drug-place conditioning, morphine mice displayed robust place preference that was attenuated by 10 mg/kg cannabidiol. Further, when administered alone, this dose of cannabidiol was void of rewarding and aversive properties. The finding that cannabidiol blocks opioid reward suggests that this compound may be useful in addiction treatment settings.
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- 2017
7. The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification
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Jessica M. Carpenter, Jonathan R. Black, Hannah M. Harris, Kenneth J. Sufka, and Todd A. Smitherman
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Male ,0301 basic medicine ,Photophobia ,Endpoint Determination ,Migraine Disorders ,medicine.medical_treatment ,Tactile Allodynia ,Sensitivity and Specificity ,Drug Administration Schedule ,Nitroglycerin Injection ,Rats, Sprague-Dawley ,Nitroglycerin ,03 medical and health sciences ,0302 clinical medicine ,Species Specificity ,Outcome Assessment, Health Care ,medicine ,Animals ,Facial pain ,Saline ,General Neuroscience ,Reproducibility of Results ,medicine.disease ,Rats ,Disease Models, Animal ,Treatment Outcome ,030104 developmental biology ,Allodynia ,Migraine ,Hyperalgesia ,Anesthesia ,medicine.symptom ,Hypoactivity ,Psychology ,030217 neurology & neurosurgery - Abstract
Background Rodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance. New method Rats received 5 nitroglycerin (10 mg/kg/2 ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15 days. Behavioral endpoints were assessed 110 min post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia. Results Animals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode. Comparison with existing methods Most NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia. Conclusions This repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints.
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- 2017
8. Effects of nalfurafine on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone: modeling an abuse-deterrent opioid analgesic in rats
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Hina N. Qureshi, Kenneth J. Sufka, Jussara M. do Carmo, Coco N. Kapanda, Hunter W. McLendon, Fernanda S. da Silva, John E. Hall, S. Stevens Negus, Jennifer E. Naylor, E. Andrew Townsend, Kevin B. Freeman, Shelley R. Edwards, and Christopher R. McCurdy
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Male ,Nociception ,0301 basic medicine ,Agonist ,medicine.drug_class ,Receptors, Opioid, mu ,Self Administration ,Pharmacology ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Spiro Compounds ,Analgesics ,Dose-Response Relationship, Drug ,business.industry ,Respiration ,Opioid-Related Disorders ,Rats ,Analgesics, Opioid ,030104 developmental biology ,Morphinans ,Opioid ,Models, Animal ,Depressant ,μ-opioid receptor ,Self-administration ,business ,Reinforcement, Psychology ,Oxycodone ,030217 neurology & neurosurgery ,Nalfurafine ,medicine.drug - Abstract
Strategies to reduce the misuse of mu opioid agonists are critically needed. Previous work has shown that kappa opioid agonists can diminish the abuse-related effects and augment the antinociceptive effects of mu agonists. However, use of traditional kappa agonists is limited by their dysphoric side effects. The current study examined the effects of nalfurafine, a clinically available atypical kappa agonist, on the reinforcing, thermal antinociceptive, and respiratory-depressant effects of oxycodone in male rats. To determine oxycodone/nalfurafine mixture proportions to be examined intravenously across procedures, a progressive ratio (PR) self-administration procedure compared the reinforcing effects of oxycodone (56 μg/kg/inj) available alone or as a mixture with co-administered nalfurafine (0.32, 1, or 3.2 μg/kg/inj), corresponding to oxycodone/nalfurafine proportions of 175:1, 56:1, and 18:1, respectively. Next, PR and thermal antinociception dose-effect functions were each determined for oxycodone, nalfurafine, and the same oxycodone/nalfurafine mixture proportions. Finally, the respiratory-depressant effects of equi-antinociceptive doses of oxycodone, nalfurafine, and the mixtures were compared. Nalfurafine decreased the reinforcing effects of oxycodone, and the 18:1 mixture did not function as a reinforcer. Oxycodone and nalfurafine each produced dose-dependent antinociception, and the mixtures produced additive antinociception. In addition, antinociceptive doses of the 56:1 and 18:1 mixtures did not produce respiratory depression. These results suggest that nalfurafine may augment the thermal antinociceptive effects while reducing the reinforcing and respiratory-depressant effects of oxycodone.
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- 2017
9. Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats
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Mahmoud A. ElSohly, Hannah M. Harris, Amira S. Wanas, Sylvia Caldwell, Kenneth J. Sufka, Mohamed M. Radwan, and Margaret A Rousseau
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Pharmacology ,biology ,Traditional medicine ,business.industry ,Analgesic ,food and beverages ,biology.organism_classification ,Cannabis sativa ,Terpene ,Nociception ,Complementary and alternative medicine ,Medicine ,Pharmacology (medical) ,Cannabis ,business ,Original Research - Abstract
Introduction: Cannabis sativa has been used for centuries in treating pain. However, the analgesic role of many of its constituents including terpenes is unknown. This research examined the contributions of terpenes (volatile oil) and cannabinoids in cannabis-mediated analgesia in rats. Methods: Animals received intraperitoneal administration of either vehicle, 10.0 or 18.0 mg/kg morphine, or various doses of the extract without terpenes, isolated terpenes, Δ(9)-tetrahydrocannabinol (THC), or the full extract. Thirty minutes later animals were tested on hotplate and tail-flick tests of thermal nociception. One week later, rats received a second administration of test articles and were tested 30 min later in the abdominal writhing test of inflammatory nociception. Results: In the thermal assays, hotplate and tail-flick latencies for morphine-treated rats were dose dependent and significantly higher than vehicle-treated animals. All the cannabinoid compounds except for the isolated terpenes produced dose-dependent increases in hotplate and tail-flick latencies. In the inflammatory nociceptive assay, animals treated with vehicle and isolated terpenes demonstrated increased abdominal writhing, whereas all the cannabinoid compounds significantly decreased abdominal writhing responses. Conclusions: Overall, THC alone produced robust analgesia equivalent to the full cannabis extract, whereas terpenes alone did not produce analgesia. These data suggest the analgesic activity of cannabis is largely mediated by THC, whereas terpenes alone do not cause alterations in cannabis-mediated analgesia.
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- 2019
10. Comparative effects of Mitragyna speciosa extract, mitragynine, and opioid agonists on thermal nociception in rats
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Ikhlas A. Khan, Helaina K. Craig, Jessica M. Carpenter, Catherine A. Criddle, Kenneth J. Sufka, Zulfiqar Ali, and Zhihao Zhang
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Male ,Nociception ,0301 basic medicine ,Agonist ,medicine.drug_class ,Mitragyna speciosa ,Mitragyna ,Pharmacology ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Morphine ,biology ,Plant Extracts ,business.industry ,General Medicine ,biology.organism_classification ,Secologanin Tryptamine Alkaloids ,Rats ,Analgesics, Opioid ,030104 developmental biology ,Opioid ,chemistry ,Mitragynine ,business ,Oxycodone ,030217 neurology & neurosurgery ,medicine.drug - Abstract
This study sought to compare the effects of Mitragyna speciosa (Korth.) Havil. extract, alkaloids fraction, and mitragynine, a μ-opioid receptor agonist, to that of morphine and oxycodone in a test of thermal nociception. In Experiment 1, male Sprague-Dawley rats were administered test articles intraperitoneally (IP) 30 min prior to testing to compare the effects of M. speciosa articles to opioid reference compounds on the hotplate assay. Test articles were vehicle, 10 mg/kg morphine, 3 mg/kg oxycodone, 300 mg/kg M. speciosa extract, 75 mg/kg M. speciosa alkaloids fraction, or 30 mg/kg mitragynine. To mirror consumer usage, Experiment 2 sought to determine whether M. speciosa articles retained their biological activity when given orally (PO). Test articles were vehicle, 6 mg/kg oxycodone, 300 mg/kg M. speciosa extract, or 100mg/kg mitragynine with hotplate tests conducted 30 and 60 min after administration. Mitragynine produced antinociceptive effects similar to the reference opioid agonists when administered IP and PO routes. These data suggest that M. speciosa extracts containing significant quantities of mitragynine may warrant consideration for further studies in primate self-administration models to yield insight into the abuse liability of this commercially available product.
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- 2016
11. Design, synthesis and biological evaluation of bivalent benzoxazolone and benzothiazolone ligands as potential anti-inflammatory/analgesic agents
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Shabana I. Khan, Ahmed H. Abdelazeem, Stephen W. White, Kenneth J. Sufka, and Christopher R. McCurdy
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Swine ,medicine.drug_class ,Stereochemistry ,Clinical Biochemistry ,Nitric Oxide Synthase Type II ,Pharmaceutical Science ,Carrageenan ,Kidney ,Biochemistry ,Article ,Anti-inflammatory ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Chlorocebus aethiops ,Drug Discovery ,medicine ,Animals ,Edema ,Humans ,Structure–activity relationship ,Benzothiazoles ,Cytotoxicity ,Vero Cells ,Molecular Biology ,Analgesics ,Benzoxazoles ,biology ,Chemistry ,Macrophages ,Anti-Inflammatory Agents, Non-Steroidal ,Organic Chemistry ,NF-kappa B ,Epithelial Cells ,In vitro ,Hindlimb ,Rats ,Molecular Docking Simulation ,Nitric oxide synthase ,Piperazine ,Drug Design ,biology.protein ,Molecular Medicine ,Dimerization - Abstract
Benzoxazolone and benzothiazolone were used as template blocks to develop two series of dimers as anti-inflammatory and analgesic agents based on the concept of bivalent ligands. The first series (I) involved varying the carbon chain lengths extending from the piperazine core to the nitrogen atom of the dibenzo[d]oxazol-2(3H)-one or dibenzo[d]thiazol-2(3H)-one. The second series (II) was designed by changing the attachment point. All compounds were screened for their in vitro anti-inflammatory activity in terms of the inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB). Seventeen compounds inhibited both targets. Eleven of them exhibited IC50 values below 3 μM while five compounds showed IC50 values of 1 μM or below. Most of the compounds were found to be devoid of cytotoxicity against mammalian kidney and solid tumors cell lines up to 25 μg/mL. In vivo anti-inflammatory and antinociceptive studies revealed that compounds 3j, 5t and 8b have significant anti-inflammatory and analgesic activity comparable to that of indomethacin and ketorolac, respectively.
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- 2015
12. The effect of Salvia divinorum and Mitragyna speciosa extracts, fraction and major constituents on place aversion and place preference in rats
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Jordan K. Zjawiony, Kenneth J. Sufka, N Abe, Ikhlas A. Khan, Melissa J. Loria, Zulfiqar Ali, and Kevin Lewellyn
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Male ,Mitragyna speciosa ,Pharmacology ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Preference test ,Drug Discovery ,Haloperidol ,Animals ,Hypnotics and Sedatives ,Medicine ,Salvia ,Habituation ,Amphetamine ,Behavior, Animal ,Dose-Response Relationship, Drug ,biology ,Mitragyna ,Plant Extracts ,business.industry ,biology.organism_classification ,Salvinorin A ,Rats ,chemistry ,Mitragynine ,Salvia divinorum ,business ,medicine.drug - Abstract
Ethnopharmacological relevance Consumer use of botanicals has increased despite, in many instances, the paucity of research demonstrating efficacy or identifying liabilities. This research employed the place preference/aversion paradigm to characterize the psychoactive properties of Salvia divinorum extract (10, 30, 100 mg/kg), salvinorin A (0.1, 0.3, 1.0 mg/kg), Mitragyna speciosa MeOH extract (50, 100, 300 mg/kg), Mitragyna speciosa alkaloid-enriched fraction (12.5, 25, 75 mg/kg) and mitragynine (5, 10, 30 mg/kg) in rats. Material and methods Following apparatus habituation and baseline preference scores, male Sprague-Dawley rats were given eight counter-balanced drug versus vehicle conditioning trials followed by a preference test conducted under drug-free states. S ( + )-amphetamine (1 mg/kg) served as the positive control (in Exp. 2) and haloperidol (0.8, 1.0 mg/kg) served as the negative control in both studies. Results Rats displayed place aversion to both Salvia divinorum and salvinorin A that exceeded that of haloperidol. Rats showed place preference to mitragynine that was similar to that of S ( + ) - amphetamine. This CPP effect was much less pronounced with the Mitragyna speciosa extract and its fraction. Conclusions These findings suggest that both botanicals possess liabilities, albeit somewhat different, that warrant caution in their use.
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- 2014
13. Strain vulnerability and resiliency in the chick anxiety–depression model
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Amy L. Salmeto, Stephen W. White, Kenneth J. Sufka, Melissa J. Loria, and Kristen A. Hymel
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Veterinary medicine ,Strain (chemistry) ,Depression ,Anxiety depression ,Experimental and Cognitive Psychology ,Anxiety ,Resilience, Psychological ,Developmental psychology ,Fight-or-flight response ,Behavioral Neuroscience ,Animal model ,Social Isolation ,Species Specificity ,Animals ,Distress vocalization ,Vocalization, Animal ,Psychology ,Chickens ,Stress, Psychological ,Depression (differential diagnoses) - Abstract
Increasing research is focused on genetic contributions to variability in stress-related endophenotypes in humans and animal model simulations. The current study sought to identify strain vulnerabilities and resiliencies to an isolation-stressor in the chick anxiety–depression model. Nine different strains of socially raised chicks were tested in isolated or non-isolated conditions for 90 min in which distress vocalization (DVoc) rates were collected and then transformed to depression-like phase threshold (@ 25, 50, 75 and 95%) latencies. In general, chicks in the non-isolated condition displayed relatively low DVoc rates throughout the test session, despite some variability in initial rates. Chicks in the isolated condition displayed relatively high DVoc rates in the first 3 min, indicative of an anxiety-like state, which declined by approximately 50% within 10–25 min in all strains and remained stable thereafter, indicative of a depression-like state. Contrast effects revealed that, relative to all other strains, the Black Australorp strain displayed shorter and the Producrain displayed longer depression threshold latencies, respectively. Of the remaining strains, the Silver Laced Wyandotte displayed depression thresholds that best represent an intermediate stress response. These findings identify vulnerable and resilient strains for examining depression-related endophenotypes in the chick anxiety–depression model.
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- 2013
14. Brain-derived neurotrophic factor response in vulnerable and resilient genetic lines in the chick anxiety–depression model
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S. Alexandra Robbins, Kenneth J. Sufka, Kristen A. Hymel, Stephen W. White, Melissa J. Loria, Prashanth Manda, S. Narasimha Murthy, and Amy L. Salmeto
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Male ,medicine.medical_specialty ,Period (gene) ,Synaptogenesis ,Enzyme-Linked Immunosorbent Assay ,Anxiety ,Hippocampal formation ,Hippocampus ,Behavioral Neuroscience ,Species Specificity ,Internal medicine ,medicine ,Animals ,Depression (differential diagnoses) ,Brain-derived neurotrophic factor ,Depression ,Brain-Derived Neurotrophic Factor ,Resilience, Psychological ,Distress ,Endocrinology ,Social Isolation ,Data Interpretation, Statistical ,Stress vulnerability ,Vocalization, Animal ,medicine.symptom ,Psychology ,Chickens ,Neuroscience ,Stress, Psychological - Abstract
Altered BDNF-mediated synaptogenesis is a major contributor to stress-vulnerability and depression. This study sought to determine patterns of hippocampal BDNF expression in stress-vulnerable and -resilient strains in the chick anxiety–depression model. Socially raised Black Australorp and Production Red strains were tested at 5–6 days post hatch under either 30, 60, 90, or 120 min of social separation stress; chicks tested with 2 social companions for 120 min served as controls. Distress vocalizations were recorded throughout the test session and latency to behavioral despair calculated. Following tests, bilateral hippocampal sections were harvested and analyzed via ELISA for BDNF levels. Black Australorps had shorter latencies to behavioral despair than Production Reds reflecting greater stress vulnerability. No differences were detected in BDNF levels between a No-Test and Social group within or between strains. The stress resilient Production Reds showed stable BDNF levels across the isolation test period whereas the vulnerable Black Australorps showed an increase in hippocampal BDNF levels that peaked at 90 min and declined thereafter. These findings fit well with the notion that strain-dependent stress-vulnerability reflects, in part, poor homeostatic mechanisms controlling synaptogenesis.
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- 2013
15. The effects of Sceletium tortuosum (L.) N.E. Br. extract fraction in the chick anxiety-depression model
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Kenneth J. Sufka, Emily M. Fountain, Ikhlas A. Khan, Jessica M. Carpenter, N Abe, Zulfiqar Ali, and Mary K. Jourdan
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Male ,medicine.medical_specialty ,Imipramine ,medicine.drug_class ,Anxiety depression ,Anxiety ,Anxiolytic ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Pharmacology ,Mesembryanthemum ,biology ,business.industry ,Depression ,Plant Extracts ,Alkaloid ,Sceletium tortuosum ,biology.organism_classification ,Antidepressive Agents ,030227 psychiatry ,Disease Models, Animal ,Mood ,Endocrinology ,Anesthesia ,Antidepressant ,medicine.symptom ,business ,Chickens ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Ethnopharmacological relevance Sceletium tortuosum (L.) N.E. Br. has been reported to elevate mood, reduce anxiety and stress and alleviate pain. Aim of study This study sought to examine the effects of an S. tortuosum alkaloid enriched fraction in the chick anxiety-depression model, a model that shows high predictive validity as a pharmacological screening assay. Material and methods Socially-raised male Silver Laced Wyandotte chicks (4–6 days old) were given IP vehicle, imipramine (10 mg/kg), or S. tortuosum fraction (10, 20, 30 mg/kg in Exp. 1 or 50, 75, 100 mg/kg in Exp. 2) 15 min prior to a 60 min isolation test period in which distress vocalizations (DVoc) were continuously recorded. Results Vehicle chicks displayed high DVoc rates in the anxiety phase (first 3 min). DVoc rates declined about 50% (i.e., behavioral despair) in the depression phase (30–60 min). S. tortuosum fraction at 75 and 100 mg/kg decreased DVoc rates during the anxiety phase indicative of an anxiolytic effect. Imipramine, but not S. tortuosum groups, increased DVoc rates in the depression phase indicative of an antidepressant effect. Conclusions The findings suggest that an alkaloid enriched S. tortuosum fraction may benefit some forms of stress-related disorders.
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- 2016
16. Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Cisplatin-Induced Neuropathy in Mice
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Kenneth J. Sufka, Waseem Gul, Hannah M. Harris, and Mahmoud A. ElSohly
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0301 basic medicine ,Male ,Gabapentin ,medicine.medical_treatment ,Analgesic ,Pharmaceutical Science ,Pharmacology ,Analytical Chemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Drug Discovery ,Delta-9-tetrahydrocannabinol ,medicine ,Animals ,Cannabidiol ,Dronabinol ,Cisplatin ,Analgesics ,Chemistry ,Plant Extracts ,Organic Chemistry ,Mice, Inbred C57BL ,Drug Combinations ,030104 developmental biology ,Complementary and alternative medicine ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,Molecular Medicine ,Cannabinoid ,medicine.symptom ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Sativex, a cannabinoid extract with a 1 : 1 ratio of tetrahydocannabinol and cannabidiol, has been shown to alleviate neuropathic pain associated with chemotherapy. This research examined whether tetrahydocannabinol or cannabidiol alone could attenuate or prevent cisplatin-induced tactile allodynia. In experiment 1, mice (C57BL/6) received eight administrations of 2.3 mg/kg cisplatin or saline solution IP every other day to induce tactile allodynia. Mice were then administered vehicle, 100 mg/kg gabapentin, 2 mg/kg tetrahydocannabinol, or 2 mg/kg cannabidiol IP and tested 60 min later on an electronic Von Frey. In experiment 2, prevention studies, cannabidiol (0.0, 0.5, 1.0, and 2.0 mg/kg) or tetrahydocannabinol (0.0, 0.5, 1.0, and 2.0 mg/kg) was given IP 30 min prior to cisplatin administration (2.3 or 1.0 mg/kg) utilizing a six-dose alternate day protocol. In both studies, tactile responses to the hind paws were quantified in g of force using an electronic Von Frey prior to and after the cisplatin administration protocol. Cisplatin produced a reduction in g of force indicative of neuropathy that was attenuated by gabapentin, tetrahydocannabinol, and cannabidiol but not prevented by either cannabinoid. These data demonstrate that each of the major constituents of Sativex alone can achieve analgesic effects against cisplatin neuropathy.
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- 2016
17. Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats
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Todd A. Smitherman, Ainslee P. Johnson, Rachel E. Davis, Morgan E. Davis, Kenneth J. Sufka, and Stephanie M. Staszko
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Neurology ,genetic structures ,Photophobia ,Migraine Disorders ,Vasodilator Agents ,medicine.medical_treatment ,Clinical Neurology ,Motor Activity ,Nitroglycerin ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Saline ,Migraine ,Behavior, Animal ,Sumatriptan ,business.industry ,Headache ,General Medicine ,Single injection ,Serotonin 5-HT1 Receptor Agonists ,Translational research ,medicine.disease ,eye diseases ,Rats ,Animal models ,Disease Models, Animal ,Treatment Outcome ,030104 developmental biology ,Anesthesiology and Pain Medicine ,Anesthesia ,Neurology (clinical) ,medicine.symptom ,business ,Hypoactivity ,Weight gain ,030217 neurology & neurosurgery ,Research Article ,medicine.drug - Abstract
Background This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan. Methods Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip. Results The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner. Conclusions These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.
- Published
- 2016
18. Preparing for a Career at a Research University
- Author
-
Kenneth J. Sufka
- Subjects
Medical education ,Writing skills ,Teaching skills ,Pedagogy ,Psychology - Published
- 2009
19. Hybridizing behavioral models: A possible solution to some problems in neurophenotyping research?
- Author
-
Allan V. Kalueff, Justin L. LaPorte, Dennis L. Murphy, and Kenneth J. Sufka
- Subjects
Information Services ,Pharmacology ,Data density ,Behavior ,Behavior, Animal ,Computer science ,Subject (documents) ,Animal Testing Alternatives ,Data science ,Behavioral analysis ,Disease Models, Animal ,Pharmaceutical Solutions ,Phenotype ,Research Design ,Research strategies ,Animals ,Humans ,Biological Psychiatry - Abstract
The use of batteries of single-domain tests for neurophenotyping research is a common strategy to achieve higher data density and explore different behavioral domains. This approach, however, is accompanied by several methodological challenges, briefly discussed here. As an alternative, this paper advocates the wider use of extensive "hybrid" protocols that assess multiple domains in parallel, or logically/logistically combine experimental paradigms, in a way that disproportionately maximizes the number of tested phenotypes per experimental manipulation. Several examples of this approach are given in this paper, demonstrating the potential to reduce time, cost and subject requirements for the experiments. Offering behavioral analyses that are lacking in the standard single-domain tests, such "hybrid" models enable innovative modeling of neuropsychiatric disorders by more thorough and broader investigation of complex phenotypical characteristics.
- Published
- 2008
20. Modeling the anxiety–depression continuum hypothesis in domestic fowl chicks
- Author
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Matthew W. Feltenstein, Edmund O. Acevedo, Courtney M. Cartwright, Heather E. Webb, Jason E. Warnick, and Kenneth J. Sufka
- Subjects
Male ,Imipramine ,medicine.drug_class ,Tricyclic antidepressant ,Antidepressive Agents, Tricyclic ,Anxiety ,Anxiolytic ,Chlordiazepoxide ,Developmental psychology ,medicine ,Animals ,Pharmacology ,Benzodiazepine ,Depression ,Disease Models, Animal ,Psychiatry and Mental health ,Distress ,Animals, Newborn ,Anti-Anxiety Agents ,Social Isolation ,Convergent validity ,Vocalization, Animal ,medicine.symptom ,Corticosterone ,Psychology ,Chickens ,Stress, Psychological ,medicine.drug ,Clinical psychology - Abstract
Anxiety and depression are currently classified as separate clinical syndromes despite considerable similarities in their symptoms, pathophysiological substrates and response to treatment interventions. An alternative hypothesis views anxiety and depression along a temporal continuum, a construct that the current research attempts to model in a preclinical setting. In experiment 1, socially raised domestic fowl chicks separated from conspecifics demonstrated a pattern of distress vocalizations that sequentially models anxiety-like and depressive-like states. In addition, administration of the benzodiazepine anxiolytic chlordiazepoxide and the tricyclic antidepressant imipramine provided pharmacological validation for the model in that they were capable of dissociating the anxiety-like and depressive-like states. In experiment 2, corticosterone levels were quantified across the isolation test session to provide convergent validity to the model. These findings fit well with the human clinical literature on the anxiety-depression continuum perspective, and suggest the consideration of a nosology that emphasizes the inter-relatedness of these clinical states rather than their boundaries.
- Published
- 2006
21. Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist
- Author
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Grant Smith, Kenneth J. Sufka, Christopher R. McCurdy, Marcelo J. Nieto, and Jason E. Warnick
- Subjects
Male ,Agonist ,Hot Temperature ,medicine.drug_class ,Clinical Biochemistry ,Analgesic ,Pharmacology ,Toxicology ,Biochemistry ,κ-opioid receptor ,Diterpenes, Clerodane ,Mice ,Behavioral Neuroscience ,chemistry.chemical_compound ,Reaction Time ,medicine ,Animals ,Biological Psychiatry ,Acetic Acid ,Pain Measurement ,Analgesics ,Psychotropic Drugs ,Dose-Response Relationship, Drug ,Salvinorin ,Receptors, Opioid, kappa ,Antagonist ,Nociceptors ,Naltrexone ,Salvinorin A ,Plant Leaves ,Nociception ,chemistry ,Diterpenes ,Norbinaltorphimine ,Muscle Contraction ,medicine.drug - Abstract
Salvinorin A, is a structurally unique, non-nitrogenous, kappa opioid receptor (KOP) agonist. Given the role of KOPs in analgesic processes, we set out to determine whether salvinorin A has antinociceptive activity in thermal and chemo-nociceptive assays. The tail-flick assay was employed to investigate 1) salvinorin A's (0.5, 1.0, 2.0, and 4.0 mg/kg) dose-response and time-course (10, 20, and 30 min) effects in a thermal nociceptive assay, and 2) the ability for the KOP antagonist norBNI (10.0 mg/kg) to prevent salvinorin A antinociception. The hotplate assay was utilized as a second thermal nociceptive measure to test salvinorin A's dose-response effects. The acetic acid abdominal constriction assay was used to study salvinorin A's dose-response and time-course (over 30 min) effects in a chemo-nociceptive assay. Together, these studies revealed that salvinorin A produces a dose-dependent antinociception that peaked at 10 min post-injection but rapidly returned to baseline. Additionally, pretreatment with the KOP antagonist norbinaltorphimine (norBNI) reversed salvinorin A-induced antinociception. These findings demonstrate that salvinorin A produces a KOP mediated antinociceptive effect with a short duration of action.
- Published
- 2006
22. An evolutionary account of chronic pain: Integrating the natural method in evolutionary psychology
- Author
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Kenneth J. Sufka and Derek D. Turner
- Subjects
Cognitive science ,Philosophy ,Adaptationism ,Chronic pain ,medicine ,Natural (music) ,Cognition ,Psychology ,medicine.disease ,Evolutionary psychology ,Applied Psychology ,Developmental psychology - Abstract
This paper offers an evolutionary account of chronic pain. Chronic pain is a maladaptive by-product of pain mechanisms and neural plasticity, both of which are highly adaptive. This account shows how evolutionary psychology can be integrated with Flanagan's natural method, and in a way that avoids the usual charges of panglossian adaptationism and an uncritical commitment to a modular picture of the mind. Evolutionary psychology is most promising when it adopts a bottom-up research strategy that focuses on basic affective and motivational systems (as opposed to higher cognitive functions) that are phylogenetically deep.
- Published
- 2005
23. Screening antidepressants in the chick separation-stress paradigm
- Author
-
Matthew W. Feltenstein and Kenneth J. Sufka
- Subjects
Sleep Wake Disorders ,Imipramine ,medicine.medical_specialty ,Pharmacology toxicology ,Drug Evaluation, Preclinical ,Citalopram ,medicine.disease_cause ,Bioinformatics ,Phenelzine ,Anxiety, Separation ,medicine ,Animals ,Psychological stress ,Maprotiline ,Psychiatry ,Pharmacology ,Dose-Response Relationship, Drug ,Antidepressive Agents ,Clinical research ,Anxiety ,medicine.symptom ,Psychology ,Chickens ,Stress, Psychological ,medicine.drug - Abstract
Clinical research has indicated that antidepressants are efficacious in the treatment of anxiety disorders, especially when repeatedly administered. However, few animal models of anxiety are sensitive to antidepressants, a finding that may be due to procedures limited to acute administrations.The purpose of the present research was to further validate the chick separation-stress paradigm as an animal model of anxiety by examining its sensitivity to the monoamine oxidase inhibitor (MAOI) phenelzine (6.25, 12.5, 25.0 mg/kg), the tricyclic antidepressant (TCA) imipramine (5.0, 10.0, 20.0 mg/kg), the selective serotonin reuptake inhibitor (SSRI) citalopram (1.0, 2.5, 5.0 mg/kg), and the norepinephrine reuptake inhibitor (NRI) maprotiline (5.0, 10.0, 20.0 mg/kg) under acute (no pretreatment) or repeated (3 or 6 days pretreatment) administration procedures.Following any pretreatment, 8-day-old chicks received their respective vehicle or drug probe injection 15 min before tests in either a "mirror" (low stress) or "no mirror" (high stress) condition for a 180-s isolation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation.The model was sensitive to acutely administered phenelzine (MAOI), imipramine (TCA), and maprotiline (NRI), but not citalopram (SSRI) and retained its sensitivity to these drug probes across both repeated administration procedures. None of the drug probes possessed any sedative properties.These results help extend the validity and utility of the chick separation-stress paradigm as an animal model of anxiety by demonstrating its sensitivity to antidepressants under both acute and repeated administration procedures.
- Published
- 2005
24. High-Performance Liquid Chromatographic Determination of Xanthohumol in Rat Plasma, Urine, and Fecal Samples
- Author
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Jason E. Warnick, Bharathi Avula, Matthew W. Feltenstein, Markus Ganzera, Kenneth J. Sufka, and Ikhlas A. Khan
- Subjects
Flavonoids ,Male ,Propiophenones ,Chromatography ,Chemistry ,Biological Availability ,General Medicine ,Urine ,High-performance liquid chromatography ,Rats ,Analytical Chemistry ,Bioavailability ,Feces ,chemistry.chemical_compound ,Pharmacokinetics ,Oral administration ,Blood plasma ,Xanthohumol ,Animals ,Rats, Wistar ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid - Abstract
Xanthohumol (XN) is the major prenylated flavonoid in hop plants and as such a constituent of beer. Pharmacological studies have shown that XN possesses marked antioxidant and antiproliferative effects. In order to study the resorption and metabolism of this compound, reversed-phase high-performance liquid chromatography is used for the determination of XN in rat plasma, urine, and feces. In session one, rats receive either oral or intravenous (iv) administration (20 mg/kg body weight) of XN. In session two, rats receive oral administration of 50, 100, 200, 400, and 500 mg/kg body weight XN for bioavailability studies at various dose levels. Plasma, urine, and feces are collected at varying time points and assayed for their XN content. Plasma levels of XN fell rapidly within 60 min after iv administration; no XN is detected in plasma after oral administration in either session. XN and its metabolites are excreted mainly in feces within 24 h of administration. The method is a reliable tool for performing studies of XN in different biological material.
- Published
- 2004
25. The chick separation stress paradigm: a validation study
- Author
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Kenneth J. Sufka, Matthew W. Feltenstein, Jason E. Warnick, and Amanda N. Guth
- Subjects
Male ,medicine.drug_class ,Clinical Biochemistry ,Drug Evaluation, Preclinical ,Anxiety ,Pharmacology ,Toxicology ,Biochemistry ,Anxiolytic ,Imipramine ,Buspirone ,Chlordiazepoxide ,Behavioral Neuroscience ,Anxiety, Separation ,Stereotypy ,medicine ,Animals ,False Positive Reactions ,Amphetamine ,Biological Psychiatry ,Anti-Anxiety Agents ,Anesthesia ,Meprobamate ,Sleep onset latency ,Vocalization, Animal ,medicine.symptom ,Sleep ,Psychology ,Chickens ,Stress, Psychological ,medicine.drug - Abstract
To expand the generalizability of the chick separation stress paradigm as a high-throughput anxiolytic screen, six positive drug probes (doses in mg/kg: meprobamate 15-120, pentobarbital 2.5-20.0, chlordiazepoxide 2.5-15.0, buspirone 2.5-10.0, imipramine 1-15, and clonidine 0.10-0.25) and five negative drug probes (amphetamine 0.5-4.0, scopolamine 0.2-1.6, caffeine 5-20, chlorpromazine 1-30, and haloperidol 0.03-1.00) were evaluated in the test. Seven-day-old chicks received intramuscular injections of either vehicle or drug probe 15 min prior to tests in either a mirror (low-stress) or a no-mirror (high-stress) condition for a 3-min observation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation. All positive drug probes attenuated distress vocalizations in a dose-dependent manner, except buspirone. All positive drug probes affected sleep onset latency in a dose-dependent manner, except buspirone and imipramine. In all cases, the anxiolytic-like effect of positive drug probes was greater than its sedative effect. None of the negative drug probes affected either distress vocalizations or sleep onset latency, except for the highest dose of amphetamine, which caused pronounced stereotypy. These findings demonstrate that this anxiolytic screen is sensitive to a wide range of positive pharmacological probes and insensitive to a wide range of negative pharmacological probes.
- Published
- 2004
26. Teaching receptor theory to biochemistry undergraduates
- Author
-
Marilee Benore-Parsons and Kenneth J. Sufka
- Subjects
Hemoglobin binding ,Science instruction ,Biochemistry ,Teaching method ,education ,Kinetic analysis ,Psychology ,Molecular Biology ,Receptor theory - Abstract
Receptor:ligand interactions account for numerous reactions critical to biochemistry and molecular biology. While students are typically exposed to some examples, such as hemoglobin binding of oxygen and signal transduction pathways, the topic could easily be expanded. Theory and kinetic analysis, types of receptors, and the experimental assay techniques should be included to properly prepare students for careers in research, medicine, or professional programs. In this article we offer a range of material for teaching these concepts to students.
- Published
- 2003
27. Dissociation of stress behaviors in the chick social-separation-stress procedure
- Author
-
Matthew W. Feltenstein, Kevin B. Freeman, Kenneth J. Sufka, and Nathan G Ford
- Subjects
Analysis of Variance ,medicine.medical_specialty ,Dissociation (neuropsychology) ,Novelty ,Experimental and Cognitive Psychology ,Audiology ,Handling, Psychological ,Social Environment ,Developmental psychology ,Behavioral Neuroscience ,Distress ,Nociception ,Social Isolation ,medicine ,Noxious stimulus ,Animals ,Test chamber ,Animal communication ,Vocalization, Animal ,Habituation ,Habituation, Psychophysiologic ,Psychology ,Chickens ,Stress, Psychological - Abstract
Separation from conspecifics in chicks produces an increase in distress vocalizations and a decrease in response to a noxious stimulus (stress-induced analgesia). This study questioned the relative contributions of novelty to the test chamber and social separation in mediating these stress responses. Eight-day-old chicks were tested either in isolation or in the presence of two social companions for a 3-min observation period in which distress vocalizations were recorded as well as the frequency of footlifts in response to a 50-microl injection of 0.10% formalin into the plantar surface of the footpad. In Expt. 1, chicks received six, 3-min test chamber habituation trials (vs. no habituation) one per day before testing; in Expt. 2, chicks were tested with mirrors placed in the chambers (vs. no mirrors). In both studies, isolated chicks in control groups (i.e., no habituation or no mirror) exhibited increased distress vocalizations and decreased nociceptive responses. In Expt. 1, habituation to the test chamber attenuated stress-induced analgesia but did not affect distress vocalizations. In Expt. 2, placement of mirrors in the test chamber attenuated distress vocalizations but did not affect stress-induced analgesia. These findings demonstrate a dissociation of stress behaviors in the chick social-separation-stress procedure: the stress-induced analgesia response is primarily mediated by novelty to the test apparatus while the distress vocalizations response is mediated by separation from conspecifics.
- Published
- 2002
28. [Untitled]
- Author
-
Donald D. Price and Kenneth J. Sufka
- Subjects
Nociception ,Central sensitization ,Neurochemical ,Gate control theory ,General Neuroscience ,Spinal Cord Dorsal Horn ,Neuroplasticity ,Neurophysiology ,Psychology ,Neuroscience - Abstract
It has been 35 years since the publicationMelzack and Wall's Gate Control Theory whichhypothesized that nociceptive information wassubject to dynamic regulation by mechanismslocated in the spinal cord dorsal horn thatcould ultimately lead to hyperalgesic orhypoalgesic states. This paper examines GateControl Theory in light of our currentunderstanding of the neuroanatomical,neurophysiological and neurochemical substratesof nociception and antinociception. Despiteits initial controversies, no one has proposeda more comprehensive overall theory of painmodulation or has successfully refuted most ofthe basic tenets of this theory.
- Published
- 2002
29. Effects of Sceletium tortuosum in rats
- Author
-
Kenneth J. Sufka, Ikhlas A. Khan, Zulfiqar Ali, Melissa J. Loria, and N Abe
- Subjects
Male ,Ataxia ,Analgesic ,Pain ,Pharmacology ,Indole Alkaloids ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Mesembrine ,Analgesics ,biology ,Behavior, Animal ,business.industry ,Depression ,Plant Extracts ,Sceletium tortuosum ,biology.organism_classification ,Conditioned place preference ,Antidepressive Agents ,Rats ,Disease Models, Animal ,Nociception ,chemistry ,Anesthesia ,Aizoaceae ,Antidepressant ,Anxiety ,medicine.symptom ,business - Abstract
Ethnopharmacological relevance Broad historical and current uses in addition to diverse activity on CNS targets may make Sceletium tortuosum a useful therapeutic in a variety of clinical settings. This study sought to more broadly characterize activity of Sceletium tortuosum and mesembrine in a number of common, rodent-based assays that model nociception, depression, anxiety, ataxia, and abuse liability. Materials and methods Male Sprague-Dawley were administered Sceletium tortuosum extract products and behavioral responses were evaluated in the conditioned place preference (CPP), hot plate, forced swim, elevated plus, and rotarod tests. Results and conclusions Sceletium tortuosum does not cause preference or aversion in CPP. Mesembrine appears to have analgesic properties without abuse liabilities or ataxia. The Sceletium tortuosum fraction has antidepressant properties but does produce ataxia. The ataxia may limit its usefulness as an antidepressant unless the antidepressant activity is associated with one constituent and the ataxia is associated with a separate constituent.
- Published
- 2014
30. Analgesic and Reinforcing Properties of ?9-THC-Hemisuccinate in Adjuvant-Arthritic Rats
- Author
-
Kenneth J. Sufka, Samir A. Ross, Susan L. Broom Ma, and Mahmoud A. ElSohly
- Subjects
Pharmacology ,Side effect ,business.industry ,organic chemicals ,medicine.medical_treatment ,Therapeutic effect ,Analgesic ,Suppository ,Conditioned place preference ,Nociception ,mental disorders ,Hyperalgesia ,Medicine ,Cannabinoid ,medicine.symptom ,business - Abstract
The use of ?9-THC hemisuccinate (HS) in a suppository formulation is an attempt to develop a cannabinoid possessing possible therapeutic effects with a minimal side effect profile. The purpose of this study was to investigate the antinociceptive and reinforcing effects of rectally administered ?9-THC-HS in rats. Tests were conducted in two groups of animals: Complete Freund's adjuvant-inflamed animals (CFA) and non-inflamed controls. A hotplate test was administered to index hyperalgesia and possible analgesic effects of ?9-THC-HS on thermal nociception. CFA animals demonstrated shorter latencies than non-inflamed animals. The highest dose of ?9-THC-HS produced longer hotplate latencies. Additionally, the reinforcing properties of ?9-THC-HS were evaluated using the Conditioned Place Preference (CPP) paradigm. ?9-THC-HS produced an increase in preference scores in non-inflamed animals (positive reinforcement), but did not affect preference scores in CFA animals. These data suggest that ?9-THC-HS h...
- Published
- 2001
31. Anxiolytic properties of botanical extracts in the chick social separation-stress procedure
- Author
-
J. Todd Roach, Susan L. Broom, Christy M. Wyandt, Lu Zeng, Kenneth J. Sufka, Matthew W. Feltenstein, and Walter G. Chambliss
- Subjects
Male ,medicine.drug_class ,Sedation ,Pharmacognosy ,Anxiolytic ,law.invention ,law ,Anxiety, Separation ,Alchemilla vulgaris ,medicine ,Animals ,Pain Measurement ,Pharmacology ,Plants, Medicinal ,Dose-Response Relationship, Drug ,Traditional medicine ,biology ,Plant Extracts ,business.industry ,biology.organism_classification ,Magnoliaceae ,Primula ,Rutaceae ,Anti-Anxiety Agents ,Analgesia ,medicine.symptom ,business ,Phytotherapy ,Chickens ,Stress, Psychological - Abstract
Rationale: The recent growth in sales of natural products labeled as dietary supplements in the United States has renewed scientific interest in the study of the therapeutic effects of multi-component botanical products. Objectives: This study sought to determine whether botanical extracts derived from the Rutaceae family, Acori graminei, the Magnoliaceae family, Alchemilla vulgaris and Primula veris, which had previously been identified in bioassays as having potential anxiolytic activity, were active in the chick social separation-stress procedure. Methods: Eight-day-old chicks received IP injections of test articles 30 min before being tested in the presence of two social companions or in isolation for a 3-min observation period. Dependent measures were: a) latency to adopt a ventral recumbent posture to index sedation, b) number of vocalizations to index separation-distress and c) a composite pain score (comprised of footlift frequency and footlift duration in response to 50 µl of 0.10% formalin injected into the plantar surface of the foot) to index stress-induced analgesia. Results: Proprietal extracts NPS00033 from the Rutaceae plant family and NPS00039 (Relora™) from the Magnoliaceae plant family screened positive in this chick model without causing sedation. Conclusions: These results suggest that botanical extracts Relora™ and NPS00033 may be useful in modulating anxiety states.
- Published
- 2001
32. Sensations and pain processes
- Author
-
Kenneth J. Sufka and Michael P. Lynch
- Subjects
Qualia ,Affect (psychology) ,Pain processing ,Philosophy ,Brain region ,medicine.anatomical_structure ,Pain affect ,Sensation ,medicine ,Psychology ,Neuroscience ,Applied Psychology ,Anterior cingulate cortex ,Cognitive psychology ,Neuroanatomy - Abstract
This paper discusses recent neuroscientific research that indicates a solution for what we label the ''causal problem'' of pain qualia, the problem of how the brain generates pain qualia. In particular, the data suggest that pain qualia naturally supervene on activity in a specific brain region: the anterior cingulate cortex (ACC). The first section of this paper discusses several philosophical concerns regarding the nature of pain qualia. The second section overviews the current state of knowledge regarding the neuroanatomy and physiology of pain processing. The third section highlights the recent research by Rainville et al. [(1997) Pain affect encoded in human anterior cingulate but not somatosensory cortex, Science, 277, 968-971], which suggests that pain affect is encoded in the ACC. The final section of the paper spells out exactly how these data affect the causal problem of pain qualia.
- Published
- 2000
33. [Untitled]
- Author
-
Kenneth J. Sufka
- Subjects
Nociception ,General Neuroscience ,Neuroplasticity ,Glutamate receptor ,Chronic pain ,medicine ,NMDA receptor ,Long-term potentiation ,AMPA receptor ,medicine.disease ,Psychology ,Long-term depression ,Neuroscience - Abstract
Pains that persist long after damaged tissue hasrecovered remain a perplexing phenomenon. Theseso-called chronic pains serve no useful function foran organism and, given its disabling effects, mighteven be considered maladaptive. However, a remarkablesimilarity exists between the neural bases thatunderlie the hallmark symptoms of chronic pain andthose that subserve learning and memory. Bothphenomena, wind-up in the pain literature andlong-term potentiation (LTP) in the learning andmemory literature, are forms of neuroplasticity inwhich increased neural activity leads to a longlasting increase in the excitability of neuronsthrough structural modifications at pre- andpost-synaptic sites. Moreover, the synapticmodifications of wind-up and LTP share a commonmechanism: a glutamate N-methyl-D-aspartate(NMDA) receptor interaction that initiates a calciummediated biochemical cascade that ultimately enhancessignal processing at theα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor. This paper arguesthat chronic pain, which has no adaptive value, canbe accounted for in terms of the highly adaptivephenomenon of activity-dependent neural plasticity;hence, some cases of chronic pain can beconceptualized as a memory trace in spinal neurons.
- Published
- 2000
34. Benzodiazepine receptor function in the chick social separation–stress procedure
- Author
-
G. Stennis Watson, J. Todd Roach, and Kenneth J. Sufka
- Subjects
Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Published
- 1999
35. Scoring the mouse formalin test: Validation study
- Author
-
Kenneth J. Sufka, Rebeccah E. Nothdurft, G. Stennis Watson, and Jeffrey S. Mogil
- Subjects
Formalin Test ,Validation study ,business.industry ,Statistical validation ,Analgesic ,Pharmacology ,Anesthesiology and Pain Medicine ,Biting ,Nociception ,Anesthesia ,Morphine ,Medicine ,Licking ,business ,medicine.drug - Abstract
The formalin test is a well-established model for assessing nociceptive processes and analgesic drug effects. Previous studies have provided statistical validation of optimal procedures for conducting and scoring the rat formalin test. In the mouse model, formalin concentration has been subjected to validation studies. The present research extended previous work by subjecting two additional parameters - the behaviors that should be scored and the optimal interval for second-phase formalin response - to empirical validation. Five behavioral (formalin-induced favoring, lifting, and biting/licking, rearing and locomotion) and two physiological measures (paw weight and paw thickness increases reflective of formalin-induced inflammation) were examined under four formalin concentrations (Exp. 1: 0.5, 1.0, 5.0, and 10.0%/25µl formalin) or under four morphine doses (Exp. 2: 0.0, 1.0, 5.0, and 10.0 mg/kg, s.c. with 5% formalin concentration). Multiple regression analyses defined the optimal second-phase formalin response in outbred, Swiss-Webster mice as 15-35 min post formalin injection, and revealed that the second-phase response is best characterized by the cumulative time spent biting/licking the injected paw. Finally, paw physiological measures provided convergent evidence of nociceptive and antinociceptive processes in the mouse formalin test. Copyright 1998European Federation of Chapters of the International Association for the Study of Pain.
- Published
- 1998
36. Identification of a treatment-resistant, ketamine-sensitive genetic line in the chick anxiety-depression model
- Author
-
Stephen W. White and Kenneth J. Sufka
- Subjects
medicine.medical_specialty ,Clinical Biochemistry ,Pharmacology ,Anxiety ,Toxicology ,Biochemistry ,Imipramine ,Behavioral Neuroscience ,medicine ,Animals ,Ketamine ,Psychiatry ,Maprotiline ,Biological Psychiatry ,Depression (differential diagnoses) ,Fluoxetine ,Depression ,Distress ,Disease Models, Animal ,Antidepressant ,Psychopharmacology ,Psychology ,Chickens ,medicine.drug - Abstract
The introduction of pharmacotherapies for treatment-resistant depression is hindered by translational challenges with existing preclinical screening models that fail to adequately model the clinical features of this syndrome. This research sought to screen antidepressants in two selected genetic lines previously identified as stress-vulnerable and -resilient in the chick anxiety-depression model. Separate groups of socially-raised 5–6 day-old Black Australorps (stress-vulnerable) and Production Reds (stress-resilient) were administered imipramine (0–20 mg/kg), fluoxetine (0–10 mg/kg), maprotiline (0–10 mg/kg) or ketamine 0–15 mg/kg) IP (1 ml/kg) and placed into isolation for 90 min. Distress vocalizations (DVoc) were recorded. Onset of behavioral despair and Dvoc rates during the depression-like phase (30–90 min) were calculated. Black Australorps entered behavioral despair approximately 25% faster than Productions Reds highlighting stress-vulnerability in this Black Australorp line. In the depression-like phase, Black Australorps were insensitive to imipramine and fluoxetine but sensitive to ketamine, a finding that parallels stress-vulnerable, treatment resistant depressive disorder. The chick anxiety-depression model using the Black Australorp line may prove useful in pre-clinical screening of novel antidepressant targets for use in treatment-resistant depression.
- Published
- 2013
37. In vitro structure-activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety-depression model
- Author
-
Dobroslawa Bialonska, Stephen W. White, Jordan K. Zjawiony, Kenneth J. Sufka, Melissa J. Loria, and Kevin Lewellyn
- Subjects
natural products ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,Anxiety ,Biochemistry ,Structure-Activity Relationship ,In vivo ,Drug Discovery ,Receptor, Serotonin, 5-HT2B ,Receptor, Serotonin, 5-HT2C ,Structure–activity relationship ,Animals ,Humans ,monoamine oxidase ,aplysinopsin ,Receptor ,Molecular Biology ,Monoamine Oxidase ,5-HT receptor ,Indole test ,Behavior, Animal ,Chemistry ,Depression ,Organic Chemistry ,Tryptophan ,In vitro ,Antidepressive Agents ,serotonin ,Disease Models, Animal ,depression ,Molecular Medicine ,Antidepressant ,Chickens ,Protein Binding - Abstract
Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with Ki's as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety-depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model.
- Published
- 2013
38. Evaluating Preference-Seeking and Aversive Qualities of Salvia divinorum and Mitragyna speciosa
- Author
-
Kevin Lewellyn, Jordan K. Zjawiony, Kenneth J. Sufka, Zulfiqar Ali, Hannah M. Harris, Ikhlas A. Khan, and Melissa J. Loria
- Subjects
Pharmacology ,Traditional medicine ,biology ,business.industry ,Addiction ,media_common.quotation_subject ,Mitragyna speciosa ,Organic Chemistry ,Pharmaceutical Science ,biology.organism_classification ,Conditioned place preference ,Preference ,Analytical Chemistry ,Complementary and alternative medicine ,Drug Discovery ,Salvia divinorum ,Molecular Medicine ,Medicine ,business ,media_common - Published
- 2013
39. Functional deficits following bilateral forelimb adjuvant inflammation assessed by operant methodology: Effects of indomethacin and morphine on recovery of function
- Author
-
Kenneth J. Sufka, Jiing-Ren Liou, Becky J. Brockel, and Stephen C. Fowler
- Subjects
Pharmacology ,medicine.medical_specialty ,Movement disorders ,business.industry ,medicine.medical_treatment ,Chronic pain ,Inflammation ,medicine.disease ,Surgery ,Psychiatry and Mental health ,medicine.anatomical_structure ,Anesthesia ,Morphine ,Medicine ,Pharmacology (medical) ,medicine.symptom ,Forelimb ,business ,Adjuvant ,medicine.drug - Published
- 1996
40. The effects of cocaine and nandrolone co-administration on aggression in male rats
- Author
-
W M Davis, S F Long, Kenneth J. Sufka, and M C Wilson
- Subjects
Male ,Narcotics ,Drug ,Time Factors ,medicine.drug_class ,media_common.quotation_subject ,Physiology ,Poison control ,Pharmacology ,Rats, Sprague-Dawley ,Anabolic Agents ,Cocaine ,Animals ,Nandrolone ,Medicine ,Biological Psychiatry ,media_common ,Dose-Response Relationship, Drug ,business.industry ,Local anesthetic ,Aggression ,Body Weight ,Drug Synergism ,Drug interaction ,Rats ,Dose–response relationship ,Social Isolation ,Toxicity ,Stereotyped Behavior ,medicine.symptom ,business ,medicine.drug - Abstract
1. Cocaine and anabolic-androgenic steroids are among the more commonly abused substances in selected populations. These agents, when used alone or in combination, have been reported to cause aggressive tendencies in both laboratory-based animal models and in human clinical situations. This project, using a resident-intruder paradigm, examined the effects of co-administration of cocaine and a typical anabolic-androgenic steroid, nandrolone decanoate, on the development of aggression in male Sprague-Dawley rats. 2. Dose response studies demonstrated that low dose cocaine (1 mg/kg) produced more aggression in a greater percentage of animals than for either the controls or groups receiving higher doses (up to 20 mg/kg). Initially, high intermittent doses of nandrolone (20 mg twice weekly) produced more aggression; however, low daily doses of nandrolone (2 mg) produced greater levels of aggression following 4 weeks of treatment. 3. Optimal doses of cocaine and nandrolone, when administered together, resulted in aggression scores that were not significantly different from controls or either drug singly. However, a greater percentage of animals receiving both drugs exhibited aggression than did rats receiving either drug alone. 4. These results support the interpretation that the drugs interact to produce unique effects in the development of aggression. However, the complexity and extent of the interactions is great and remains to be fully elucidated.
- Published
- 1996
41. Stimulus properties and antinociceptive effects of selective bradykinin B1 and B2 receptor antagonists in rats
- Author
-
Kenneth J. Sufka and J. Todd Roach
- Subjects
Male ,medicine.medical_treatment ,Bradykinin ,Inflammation ,Stimulus (physiology) ,Pharmacology ,Choice Behavior ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Formaldehyde ,medicine ,Animals ,Bradykinin Receptor Antagonists ,Dose-Response Relationship, Drug ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Antagonist ,Nociceptors ,Stimulation, Chemical ,Conditioned place preference ,Rats ,Anesthesiology and Pain Medicine ,Nociception ,Neurology ,B2 receptor ,chemistry ,Neurology (clinical) ,medicine.symptom ,business ,Adjuvant - Abstract
Research has documented the differential role of bradykinin (BK) B1 and B2 receptors in the mediation of inflammatory nociception and this research suggests that selective B1 antagonists may have therapeutic potential against chronic inflammatory pain. The present study sought to further define the stimulus properties (reinforcing and aversive effects) of the selective B1 antagonist des-Arg9,(Leu8)-BK (0.0, 0.03, 0.1, and 0.3 mg/kg) and the selective B2 antagonist HOE 140 (0.0, 0.1, 0.5, and 1.0 mumol/kg) in the Freund's adjuvant (100 microliters, i.p.) model of chronic inflammatory nociception using the place preference paradigm. In addition, this research examined the differential antinociceptive effects of these antagonists on the formalin test (2.5%). Des-Arg9,(Leu8)-BK exhibited antinociceptive effects against both the first and second phases of the formalin response; HOE 140 tended to increase nociceptive responding on both phases of the formalin response. In the place preference paradigm, des-Arg9,(Leu8)-BK, but not HOE 140, exhibited negatively reinforcing effects (i.e. analgesia) in adjuvant-inflamed animals and aversive effects in noninflamed control animals. Neither compound exhibited positively reinforcing effects (i.e. abuse potential). These results further define the stimulus properties of these selective BK antagonists and provide additional evidence to support the notion that B1 antagonists may possess therapeutic potential for conditions of chronic inflammatory pain.
- Published
- 1996
42. Section Review: Central & Peripheral Nervous Systems: Novel approaches for analgesic drug assessment: new animal paradigms
- Author
-
Kenneth J Sufka
- Subjects
Pharmacology ,Drug ,business.industry ,media_common.quotation_subject ,Analgesic ,Chronic pain ,General Medicine ,Inflammatory pain ,medicine.disease ,Preference ,Efficacy ,Medicine ,Pharmacology (medical) ,Operant response ,business ,Neuroscience ,media_common - Abstract
The discovery of novel therapeutics for the treatment of chronic pain depends largely upon the development of clinically-relevant animal models and quantitative methods for evaluation of drug efficacy. This paper describes our use of the place preference paradigm and the operant response paradigm to provide unique and clinically-relevant measures of analgesic drug effects against chronic inflammatory pain in rats. The data presented demonstrate that the place preference paradigm can assess the affective properties of analgesic drugs under conditions of chronic pain, and that the operant response paradigm can quantify both the functional motor deficits that accompany chronic inflammatory pain and the recovery of function afforded by analgesic drugs. These data suggest that both place preference and operant response paradigms may serve as useful assays for evaluating unique and clinically-relevant aspects of analgesic drug effects in animal models of chronic inflammatory pain.
- Published
- 1996
43. In vitro and in vivo evaluation of the antidepressant activity of aplysinopsin analogs
- Author
-
Jordan K. Zjawiony, Kevin Lewellyn, Dobroslawa Bialonska, Kenneth J. Sufka, Babu L. Tekwani, Stephen W. White, Melissa J. Loria, and Narayan D. Chaurasiya
- Subjects
Pharmacology ,Aplysinopsin ,Complementary and alternative medicine ,Chemistry ,In vivo ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Antidepressant ,In vitro ,Analytical Chemistry - Published
- 2012
44. Chick Anxiety–Depression Screening Model
- Author
-
Stephen W. White and Kenneth J. Sufka
- Subjects
business.industry ,Anxiety depression ,Medicine ,business ,Clinical psychology - Published
- 2012
45. Opiate effects of isolation stress in domestic fowl
- Author
-
James L. Borland, Richard A. Hughes, Tammy M. McCormick, and Kenneth J. Sufka
- Subjects
Male ,Narcotics ,medicine.medical_specialty ,Fever ,Clinical Biochemistry ,(+)-Naloxone ,Toxicology ,Biochemistry ,Behavioral Neuroscience ,Internal medicine ,Respiration ,medicine ,Animals ,Biological Psychiatry ,Pain Measurement ,Pharmacology ,Hypoalgesia ,Morphine ,Naloxone ,Nociceptors ,Thermoregulation ,Jump response ,Endocrinology ,Social Isolation ,Opioid ,Analgesia ,Vocalization, Animal ,Opiate ,Psychology ,Chickens ,Stress, Psychological ,medicine.drug - Abstract
In an attempt to examine the role of opioid system functioning in social attachment and isolation stress in young domestic fowl, the effects of morphine (5.0 mg/kg) and naloxone (5.0 mg/kg) were evaluated on distress vocalizations, thermal nociception, thermoregulation, and respiration following 15 min of isolation in 7-day-old White-Leghorn cockerels. Morphine decreased and naloxone increased distress vocalizations in isolated chicks. Isolation produced an increase in jump response latencies (i.e., hypoalgesia) on a standard hot-plate test. In general, morphine decreased and naloxone increased mean jump latencies in both isolated and nonisolated chicks. Isolation produced an increase in core body temperature (i.e., hyperthermia); morphine decreased and naloxone increased core body temperatures independent of the isolation manipulation. Social isolation did not affect respiration. However, morphine depressed respiration in both isolated and nonisolated chicks. These results support the notion that opioid systems modulate social attachment and isolation stress.
- Published
- 1994
46. Pharmacological reversal of cognitive bias in the chick anxiety-depression model
- Author
-
Kenneth J. Sufka and Kristen A. Hymel
- Subjects
Imipramine ,media_common.quotation_subject ,Pessimism ,Anxiety ,Clonidine ,Developmental psychology ,Cellular and Molecular Neuroscience ,Optimism ,Bias ,medicine ,Animals ,media_common ,Pharmacology ,Analysis of Variance ,Depression ,Stressor ,Cognitive bias ,Antidepressive Agents ,Disease Models, Animal ,Animals, Newborn ,Aversive Stimulus ,medicine.symptom ,Cues ,Vocalization, Animal ,Psychology ,Cognition Disorders ,Chickens ,Stress, Psychological ,medicine.drug - Abstract
Cognitive bias presents in clinical populations where anxious individuals adopt a more pessimistic interpretation of ambiguous aversive stimuli and depressed individuals adopt both a more pessimistic interpretation of ambiguous aversive stimuli and a less optimistic interpretation of ambiguous appetitive stimuli. These biases have been reversed by anxiolytics and antidepressants. In the current study, chicks exposed to an isolation stressor of 5-min to induce an anxiety-like state or 60-min to induce a depressive-like state were tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. Chicks in the depression-like state displayed more pessimistic-like and less optimistic-like approach behavior to ambiguous aversive and appetitive cues, respectively. Both forms of cognitive bias were reversed by 15.0 mg/kg imipramine. Chicks in anxiety-like state displayed more pessimistic-like approach behavior under the ambiguous aversive stimulus cues. However, 0.10 mg/kg clonidine produced modest sedation and thus, was ineffective at reversing this bias. The observation that cognitive biases of more pessimism and less optimism can be reversed in the depression-like phase by imipramine adds to the validity of the chick anxiety–depression model as a neuropsychiatric simulation. This article is part of a Special Issue entitled ‘Anxiety and Depression’.
- Published
- 2011
47. Cerebral lateralization in homosexual males: a preliminary EEG investigation
- Author
-
Joel E. Alexander and Kenneth J. Sufka
- Subjects
Adult ,Male ,medicine.medical_specialty ,Elementary cognitive task ,Alpha (ethology) ,Electroencephalography ,Audiology ,Functional Laterality ,Lateralization of brain function ,Developmental psychology ,Alpha rhythm ,Physiology (medical) ,medicine ,Humans ,medicine.diagnostic_test ,General Neuroscience ,Cerebral laterality ,Homosexuality ,Alpha Rhythm ,Neuropsychology and Physiological Psychology ,Space Perception ,Laterality ,Female ,Psychology ,Alpha power ,Psychomotor Performance - Abstract
A preliminary investigation was conducted to determine whether hemispheric patterns of electrophysiological activation in male homosexuals differ from that of male and female heterosexuals. Electroencephalographic (EEG) activity was recorded over left and right cerebral hemispheric locations while subjects performed verbal and spatial cognitive tasks. Male homosexuals demonstrated different patterns of alpha power compared to heterosexual males and females during baseline recording. Different hemispheric patterns of alpha activity also were observed between homosexual and heterosexual males during affective judgments of both verbal and spatial stimuli, but not between homosexual males and heterosexual females. These results provide further evidence of biologically-mediated functional differences between homosexuals and heterosexuals.
- Published
- 1993
48. Effects of calcitonin on CNS monoamines following carrageenan-induced inflammation in rats
- Author
-
Kenneth J. Sufka and Dean A. Hoganson
- Subjects
Calcitonin ,Male ,medicine.medical_specialty ,Clinical Biochemistry ,Central nervous system ,Carrageenan ,Toxicology ,Biochemistry ,Rats, Sprague-Dawley ,Behavioral Neuroscience ,Dopamine ,Internal medicine ,Monoaminergic ,Animals ,Medicine ,Biogenic Monoamines ,Biological Psychiatry ,Inflammation ,Pharmacology ,business.industry ,Brain ,Nociceptors ,Spinal cord ,Rats ,Endocrinology ,Nociception ,medicine.anatomical_structure ,Monoamine neurotransmitter ,Spinal Cord ,Serotonin ,business ,medicine.drug - Abstract
The present study examined the effects of systematically administered calcitonin (CT, 10 IU/0.25 ml, SC) on changes in CNS monoamines (MAs) following unilateral carrageenan (CARRA)-induced inflammation in the rat hindpaw. High-performance liquid chromatography with electrochemical detection (HPLC-EC) for MAs was performed on the whole brain and rostral spinal cord. Carrageenan-evoked inflammation significantly increased brain serotonin [5-hydroxytryptamine (5-HT)], norepinephrine (NE), and dopamine (DA) levels. CT significantly reduced these CARRA-induced elevations in brain MAs. Elevated spinal cord 5-HT and NE levels were observed in CARRA-treated animals. CT administration increased 5-HT and NE in both the CARRA-treated animals and their saline controls. Spinal cord DA levels were not affected by either CARRA or CT administration. These findings suggest the involvement of CNS monoaminergic substrates in CT-induced hypoalgesia in inflammatory nociception.
- Published
- 1993
49. Cognitive bias in the chick anxiety-depression model
- Author
-
Kenneth J. Sufka, Kristen A. Hymel, Ben O. Brilot, Erika C. Carpenter, Melissa Bateson, and Amy L. Salmeto
- Subjects
animal structures ,Endophenotypes ,Anxiety depression ,Anxiety ,Bias ,Escape Reaction ,Predictive Value of Tests ,medicine ,Reaction Time ,Animals ,Maze Learning ,Molecular Biology ,Analysis of Variance ,Behavior, Animal ,Depression ,General Neuroscience ,Stressor ,Cognition ,Cognitive bias ,Disease Models, Animal ,Endophenotype ,Neurology (clinical) ,Analysis of variance ,Aversive Stimulus ,medicine.symptom ,Cues ,Psychology ,Cognition Disorders ,Neuroscience ,Chickens ,Photic Stimulation ,Developmental Biology ,Cognitive psychology - Abstract
Cognitive bias is a phenomenon that presents in clinical populations where anxious individuals tend to adopt a more pessimistic-like interpretation of ambiguous aversive stimuli whereas depressed individuals tend to adopt a less optimistic-like interpretation of ambiguous appetitive stimuli. To further validate the chick anxiety-depression model as a neuropsychiatric simulation we sought to quantify this cognitive endophenotype. Chicks exposed to an isolation stressor of 5m to induce an anxiety-like or 60 m to induce a depressive-like state were then tested in a straight alley maze to a series of morphed ambiguous appetitive (chick silhouette) to aversive (owl silhouette) cues. In non-isolated controls, runway start and goal latencies generally increased as a function of greater amounts of aversive characteristics in the cues. In chicks in the anxiety-like state, runway latencies were increased to aversive ambiguous cues, reflecting more pessimistic-like behavior. In chicks in the depression-like state, runway latencies were increased to both aversive and appetitive ambiguous cues, reflecting more pessimistic-like and less optimistic-like behavior, respectively.
- Published
- 2010
50. Enhancement of natural killer cell activity in healthy subjects by Immulina®, a Spirulina extract enriched for Braun-type lipoproteins
- Author
-
Hemlata Tamta, Premalatha Balachandran, Xiangmei Wu, David S. Pasco, Christian Enevold, Michelle Schjørring-Thyssen, Claus Henrik Nielsen, Ole Christensen, Nirmal Pugh, Kenneth J. Sufka, and Anette Walsted
- Subjects
Adult ,Male ,Natural Killer Cell Activity ,Lipoproteins ,T-Lymphocytes ,Pharmaceutical Science ,Pilot Projects ,Biology ,Lymphocyte Activation ,Analytical Chemistry ,Cell activity ,Young Adult ,Adjuvants, Immunologic ,Double-Blind Method ,Reference Values ,Cell Line, Tumor ,Drug Discovery ,medicine ,Spirulina ,Humans ,RNA, Messenger ,Aged ,Pharmacology ,Cross-Over Studies ,Dose-Response Relationship, Drug ,Activator (genetics) ,Perforin ,Plant Extracts ,Monocyte ,Organic Chemistry ,Healthy subjects ,Middle Aged ,biology.organism_classification ,Molecular biology ,Antineoplastic Agents, Phytogenic ,In vitro ,Killer Cells, Natural ,medicine.anatomical_structure ,Complementary and alternative medicine ,NK Cell Lectin-Like Receptor Subfamily K ,Immunology ,Dietary Supplements ,Leukocytes, Mononuclear ,Molecular Medicine ,Female ,Leukemia, Erythroblastic, Acute ,Arthrospira ,Biomarkers ,Phytotherapy - Abstract
Immulina®, a commercial extract of Arthrospira (Spirulina) platensis is a potent activator of THP-1 monocytes and CD4+ T cells IN VITRO and enhances several immunological functions in mice. We further characterized Immulina® by determining that Braun-type lipoproteins are responsible for a major portion of the IN VITRO monocyte activation exhibited by this material. In order to understand the effect of Immulina® on NK cell activity, a pilot study was conducted on ten healthy North American individuals who supplemented their diet with Immulina® (400 mg/day) for seven days. We observed a 40% average increase in the killing of K562 tumor cells by NK cells (p 0.01) after Immulina® supplementation. In a separate placebo-controlled, crossover study involving 11 healthy Danish subjects, we observed increased mRNA expression of the NK cell marker NKG2D by 37% (p = 0.02) and by 55% (p = 0.0003) after administration of Immulina® (200 mg and 400 mg per day, respectively) for seven days. The mRNA expression of the NK- and T-cell marker perforin increased by 75% (p = 0.008) after administration of 400 mg Immulina® per day. Both markers displayed significant dose-dependent effects (p = 0.0003 and p = 0.02, respectively). The ratio between CD56 (bright) and CD56 (dim) NK cells was not affected by Immulina® administration. In summary, two independent studies showed enhancement of NK cell activity following administration of Immulina® for seven days.
- Published
- 2010
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