22 results on '"Ignatowska-Jankowska B"'
Search Results
2. In vivo characterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects
- Author
-
Ignatowska-Jankowska, B M, Ghosh, S, Crowe, M S, Kinsey, S G, Niphakis, M J, Abdullah, R A, Tao, Q, Oʼ Neal, S T, Walentiny, D M, Wiley, J L, Cravatt, B F, and Lichtman, A H
- Published
- 2014
- Full Text
- View/download PDF
3. The novel, orally available and peripherally restricted selective cannabinoid CB2 receptor agonist LEI-101 prevents cisplatin-induced nephrotoxicity
- Author
-
Mukhopadhyay, P., Baggelaar, M., Erdelyi, K., Cao, Z., Cinar, R., Fezza, F., Ignatowska-Jankowska, B., Wilkerson, J., Gils, N. van, Hansen, T., Ruben, M., Soethoudt, M., Heitman, L., Kunos, G., Maccarrone, M., Lichtman, A., Pacher, P., Stelt, M. van der, Chemistry and Pharmaceutical Sciences, and Hematology laboratory
- Subjects
Oral ,Male ,Knockout ,Morpholines ,Apoptosis ,CHO Cells ,DNA Fragmentation ,Administration, Oral ,Animals ,Cisplatin ,Cricetulus ,Imidazolidines ,Kidney ,Kidney Diseases ,Lipid Peroxidation ,Mice, Inbred C57BL ,Mice, Inbred ICR ,Mice, Knockout ,Protective Agents ,Reactive Oxygen Species ,Receptor, Cannabinoid, CB2 ,Inbred C57BL ,Mice ,SDG 3 - Good Health and Well-being ,Settore BIO/10 ,Cannabinoid ,Inbred ICR ,CB2 ,Administration ,Receptor - Abstract
Background and Purpose Here, we have characterized 3-cyclopropyl-1-(4-(6-((1,1-dioxidothiomorpholino)methyl)-5-fluoropyridin-2-yl)benzyl)imidazolidine-2,4-dione hydrochloride (LEI-101) as a novel, peripherally restricted cannabinoid CB2 receptor agonist, using both in vitro and in vivo models. Experimental Approach We investigated the effects of LEI-101 on binding and functional activity. We assessed its in vitro and in vivo selectivity. Efficacy of LEI-101 was determined in a mouse model of cisplatin-induced nephrotoxicity. Key Results LEI-101 behaved as a partial agonist at CB2 receptors using β-arrestin and GTPγS assays and was ~100-fold selective in CB2 /CB1 receptor-binding assays. It did not display any activity on endocannabinoid hydrolases and nor did it react with serine hydrolases in an activity-based protein profiling assay. In mice, LEI-101 had excellent oral bioavailability reaching high concentrations in the kidney and liver with minimal penetration into the brain. LEI-101 up to a dose of 60 mg·kg-1 (p.o.) did not exert any CNS-mediated effects in the tetrad assay, in mice. LEI-101 (p.o. or i.p.) at 3 or 10 mg·kg-1 dose-dependently prevented kidney dysfunction and/or morphological damage induced by cisplatin in mice. These protective effects were associated with improved renal histopathology, attenuated oxidative stress and inflammation in the kidney. These effects were absent in CB2 receptor knockout mice. Conclusion and Implications These results indicate that LEI-101 is a selective, largely peripherally restricted, orally available CB2 receptor agonist with therapeutic potential in diseases that are associated with inflammation and/or oxidative stress, including kidney disease.
- Published
- 2016
4. Discriminative Stimulus Properties of the Endocannabinoid Catabolic Enzyme Inhibitor SA-57 in Mice
- Author
-
Owens, R. A., primary, Ignatowska-Jankowska, B., additional, Mustafa, M., additional, Beardsley, P. M., additional, Wiley, J. L., additional, Jali, A., additional, Selley, D. E., additional, Niphakis, M. J., additional, Cravatt, B. F., additional, and Lichtman, A. H., additional
- Published
- 2016
- Full Text
- View/download PDF
5. HPLC-MS-MS Determination of ZCZ-011, A Novel Pharmacological Tool for Investigation of the Cannabinoid Receptor in Mouse Brain Using Clean Screen FASt Column Extraction
- Author
-
Poklis, J. L., primary, Clay, D. J., additional, Ignatowska-Jankowska, B. M., additional, Zanato, C., additional, Ross, R. A., additional, Greig, I. R., additional, Abdullah, R. A., additional, Mustafa, M. A., additional, Lichtman, A. H., additional, and Poklis, A., additional
- Published
- 2015
- Full Text
- View/download PDF
6. In vivocharacterization of the highly selective monoacylglycerol lipase inhibitor KML29: antinociceptive activity without cannabimimetic side effects
- Author
-
Ignatowska-Jankowska, B M, primary, Ghosh, S, additional, Crowe, M S, additional, Kinsey, S G, additional, Niphakis, M J, additional, Abdullah, R A, additional, Tao, Q, additional, O' Neal, S T, additional, Walentiny, D M, additional, Wiley, J L, additional, Cravatt, B F, additional, and Lichtman, A H, additional
- Published
- 2014
- Full Text
- View/download PDF
7. P.6.d.021 Cannabinoid CB2 receptor antagonist prevents cannabidiol-induced decrease in body weight gains in rats
- Author
-
Ignatowska-Jankowska, B., primary, Jankowski, M.M., additional, Glac, W., additional, and Swiergiel, A.H., additional
- Published
- 2010
- Full Text
- View/download PDF
8. P.6.d.020 Dose-dependent effects of repeated intravenous cocaine on CD4:CD8 lymphocyte ratio in peripheral blood of rats
- Author
-
Jankowski, M.M., primary, Ignatowska-Jankowska, B., additional, Glac, W., additional, and Swiergiel, A.H., additional
- Published
- 2010
- Full Text
- View/download PDF
9. P.1.c.002 Cannabidiol lowers body weight gains in rats
- Author
-
Ignatowska-Jankowska, B., primary, Jankowski, M., additional, Glac, W., additional, and Swiergiel, A.H., additional
- Published
- 2009
- Full Text
- View/download PDF
10. P.1.c.029 Acute and chronic exposure to intravenous cocaine affects lymphocyte subsets distribution in peripheral blood of rats
- Author
-
Jankowski, M., primary, Ignatowska-Jankowska, B., additional, Glac, W., additional, and Swiergiel, A.H., additional
- Published
- 2009
- Full Text
- View/download PDF
11. P55 UNILATERAL LESION OF THE MESOLIMBIC TARGET STRUCTURE INFLUENCES BEHAVIORAL RESPONSE TO ACTIVATION OF ITS CONTRALATERAL SOMATODENDRITIC AREA.
- Author
-
Pluci??ska, K., primary, Jankowski, M., additional, Ignatowska-Jankowska, B., additional, and Trojniar, W., additional
- Published
- 2006
- Full Text
- View/download PDF
12. Cannabidiol-induced lymphopenia does not involve NKT and NK cells
- Author
-
Ignatowska-Jankowska B, Jankowski M, Wojciech Glac, and Ah, Swiergel
- Subjects
Killer Cells, Natural ,Male ,Dose-Response Relationship, Drug ,Lymphopenia ,Animals ,Cannabidiol ,Immunologic Factors ,Natural Killer T-Cells ,Lymphocyte Subsets ,Rats - Abstract
The major non-psychoactive compound of cannabis plant, cannabidiol, has been reported to be a promising therapeutic agent for many inflammatory, autoimmune and neurodegenerative diseases. In spite of growing interest in therapeutic use of cannabidiol very little is known about its influence on the immune system. Present study aimed to evaluate lymphocyte subsets distribution in peripheral blood after repeated, systemic administration of cannabidiol. Adult male Wistar rats received intraperitoneal injections of vehicle or cannabidiol at dose of 2.5 or 5 mg/kg/day, for 14 consecutive days. Blood samples were collected one hour after the last injection. Three-color immunofluorescent antibody staining procedure (CD3-FITC/CD45RA-PC7/CD161A-APC and CD3-FITC/CD4-PC7/CD8-APC) was used for determination of T, B, NK, NKT, T helper, and T cytotoxic lymphocyte subsets. Total leukocyte number and percentage numbers of leukocyte subpopulations were also assessed. Administration of cannabidiol at dose of 5 mg/kg caused a significant decrease in total leukocyte number and a significant fall in total numbers of T, B, and both T helper and T cytotoxic lymphocyte subsets. This immunosuppressive effect did not affect the total numbers of NK and NKT cells that are responsible for the primary, nonspecific antiviral and antitumor immune response. In contrast, administration of cannabidiol at dose of 2.5 mg/kg increased the total and percentage NKT cells numbers, and the percentage number of NK cells. The results suggest that repeated treatment with cannabidiol inhibits specific immunity by reduction of T, B, T cytotoxic, and T helper cell numbers, and may enhance nonspecific antiviral and antitumor immune response related to NK and NKT cells.
13. In vivo evaluation of the CB 1 allosteric modulator LDK1258 reveals CB 1 -receptor independent behavioral effects.
- Author
-
Mustafa M, Donvito G, Moncayo L, Swafford A, Poklis J, Grauer R, Olszewska T, Ignatowska-Jankowska B, Kendall DA, Lu D, and Lichtman AH
- Subjects
- Allosteric Regulation, Amidohydrolases genetics, Animals, Arachidonic Acids pharmacology, Cannabinoid Receptor Agonists pharmacology, Cannabinoid Receptor Antagonists pharmacology, Chromatography, Liquid, Cyclohexanols pharmacology, Disease Models, Animal, Endocannabinoids pharmacology, Female, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Polyunsaturated Alkamides pharmacology, Receptor, Cannabinoid, CB1 genetics, Rimonabant pharmacology, Tandem Mass Spectrometry, Analgesics pharmacology, Appetite Depressants pharmacology, Behavior, Animal drug effects, Locomotion drug effects, Neuralgia drug therapy, Receptor, Cannabinoid, CB1 metabolism
- Abstract
In the present study, we examined whether LDK1258, which produces strong CB
1 receptor allosteric effects in in vitro assays, would elicit in vivo effects consistent with allosteric activity. In initial studies, LDK1258 reduced food consumption and elicited delayed antinociceptive effects in the chronic constrictive injury of the sciatic nerve (CCI) model of neuropathic pain, which unexpectedly emerged 4 h post-injection. UPLC-MS/MS analysis quantified significant levels of LDK1258 in both blood and brain tissue at 30 min post-administration that remained stable up to 4 h. The observation that LDK1258 also produced respective antinociceptive and anorectic effects in rimonabant-treated wild type mice and CB1 (-/-) mice suggests an off-target mechanism of action. Likewise, LDK1258 produced a partial array of common cannabimimetic effects in the tetrad assay, which were not CB1 receptor mediated. Additionally, LDK1258 did not substitute for the CB1 receptor orthosteric agonists CP55,940 or anandamide in the drug discrimination paradigm. In other in vivo assays sensitive to CB1 receptor allosteric modulators, LDK1258 failed to shift the dose-response curves of either CP55,940 or anandamide in producing thermal antinociception, catalepsy, or hypothermia, and did not alter the generalization curve of either drug in the drug discrimination assay. Thus, this battery of tests yielded results demonstrating that LDK1258 produces antinociceptive effects in the CCI model of neuropathic pain, anorectic effects, and other in vivo pharmacological effects in a manner inconsistent with CB1 receptor allosterism. More generally, this study offers a straightforward screening assay to determine whether newly synthesized CB1 receptor allosteric modulators translate to the whole animal., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
14. Endocannabinoids exert CB 1 receptor-mediated neuroprotective effects in models of neuronal damage induced by HIV-1 Tat protein.
- Author
-
Xu C, Hermes DJ, Nwanguma B, Jacobs IR, Mackie K, Mukhopadhyay S, Lichtman AH, Ignatowska-Jankowska B, and Fitting S
- Subjects
- Animals, Calcium metabolism, Cannabinoid Receptor Antagonists pharmacology, Cell Survival, Cells, Cultured, Mice, Mice, Inbred C57BL, Neurons metabolism, Neurons physiology, Piperidines pharmacology, Polyunsaturated Alkamides, Prefrontal Cortex cytology, Pyrazoles pharmacology, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Receptor, Cannabinoid, CB1 metabolism, Rimonabant, Synaptic Transmission, tat Gene Products, Human Immunodeficiency Virus toxicity, Arachidonic Acids pharmacology, Endocannabinoids pharmacology, Glycerides pharmacology, Neurons drug effects, Neuroprotective Agents pharmacology, Receptor, Cannabinoid, CB1 agonists
- Abstract
In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND. Consequently, we tested whether the eCBs N-arachidonoylethanolamine (anandamide/AEA) and 2-arachidonoyl-glycerol (2-AG) offer neuroprotective actions in a neuronal culture model. Specifically, we examined the neuroprotective actions of these eCBs on Tat excitotoxicity in primary cultures of prefrontal cortex neurons (PFC), and whether cannabinoid receptors mediate this neuroprotection. Tat-induced excitotoxicity was reflected by increased intracellular calcium levels, synaptodendritic damage, neuronal excitability, and neuronal death. Further, upregulation of cannabinoid 1 receptor (CB
1 R) protein levels was noted in the presence of HIV-1 Tat. The direct application of AEA and 2-AG reduced excitotoxic levels of intracellular calcium and promoted neuronal survival following Tat exposure, which was prevented by the CB1 R antagonist rimonabant, but not by the CB2 R antagonist AM630. Overall, our findings indicate that eCBs protect PFC neurons from Tat excitotoxicity in vitro via a CB1 R-related mechanism. Thus, the eCB system possesses promising targets for treatment of neurodegenerative disorders associated with HIV-1 infection., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
15. Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497.
- Author
-
Grim TW, Samano KL, Ignatowska-Jankowska B, Tao Q, Sim-Selly LJ, Selley DE, Wise LE, Poklis A, and Lichtman AH
- Subjects
- Animals, Cannabinoid Receptor Antagonists pharmacology, Dronabinol pharmacology, Drug Tolerance, Endocannabinoids pharmacology, Female, GTP-Binding Proteins metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, Piperidines pharmacology, Pyrazoles pharmacology, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Rimonabant, Cannabinoids pharmacology
- Abstract
A series of in vivo and in vitro assays were conducted to characterize the pharmacological effects of the first generation abused synthetic cannabinoid CP47,497, a racemic bicyclic cannabinoid that is similar in structure to the potent, high-efficacy synthetic cannabinoid CP55,940. CP47,497 was less efficacious than CP55,940 in activating G-proteins and dose-dependently produced common CB1 receptor-dependent pharmacological effects (i.e. catalepsy, hypothermia, antinociception, and hypolocomotion). CP47,497 also substituted for Δ9-tetrahydrocannabinol (THC) in the mouse drug discrimination, indicating that both drugs elicited a similar interceptive stimulus. The pharmacological effects of CP47,497 underwent tolerance following repeated administration and showed cross-tolerance following repeated THC administration, further suggesting a common cannabimimetic mechanism of action. Finally, the CB1 receptor antagonist rimonabant precipitated similar magnitudes of somatic withdrawal responses in mice treated repeatedly with THC or CP47,497. Taken together, these data verify the acute cannabimimetic effects of CP47,497, and indicate tolerance and dependence following repeated administration. The assays used here provide a straightforward approach to characterize the emerging next generation of abused synthetic cannabinoids.
- Published
- 2016
- Full Text
- View/download PDF
16. Selective monoacylglycerol lipase inhibitors: antinociceptive versus cannabimimetic effects in mice.
- Author
-
Ignatowska-Jankowska B, Wilkerson JL, Mustafa M, Abdullah R, Niphakis M, Wiley JL, Cravatt BF, and Lichtman AH
- Subjects
- Analgesics therapeutic use, Animals, Benzodioxoles pharmacology, Benzodioxoles therapeutic use, Biomimetic Materials therapeutic use, Brain drug effects, Brain metabolism, Carbamates pharmacology, Carbamates therapeutic use, Constriction, Endocannabinoids metabolism, Enzyme Inhibitors therapeutic use, Hyperalgesia drug therapy, Hyperalgesia etiology, Male, Mice, Mice, Inbred C57BL, Motor Activity drug effects, Neuralgia drug therapy, Neuralgia etiology, Piperidines pharmacology, Piperidines therapeutic use, Succinimides pharmacology, Succinimides therapeutic use, Analgesics pharmacology, Biomimetic Materials pharmacology, Cannabinoids metabolism, Enzyme Inhibitors pharmacology, Monoacylglycerol Lipases antagonists & inhibitors
- Abstract
The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) plays an important role in a variety of physiologic processes, but its rapid breakdown by monoacylglycerol lipase (MAGL) results in short-lived actions. Initial MAGL inhibitors were limited by poor selectivity and low potency. In this study, we tested JZL184 [4-nitrophenyl 4-[bis(2H-1,3-benzodioxol-5-yl)(hydroxy)methyl]piperidine-1-carboxylate] and MJN110 [2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate], MAGL inhibitors that possess increased selectivity and potency, in mouse behavioral assays of neuropathic pain [chronic constriction injury (CCI) of the sciatic nerve], interoceptive cannabimimetic effects (drug-discrimination paradigm), and locomotor activity in an open field test. MJN110 (1.25 and 2.5 mg/kg) and JZL184 (16 and 40 mg/kg) significantly elevated 2-AG and decreased arachidonic acid but did not affect anandamide in whole brains. Both MAGL inhibitors significantly reduced CCI-induced mechanical allodynia with the following potencies [ED50 (95% confidence limit [CL]) values in mg/kg: MJN110 (0.43 [0.30-0.63]) > JZL184 (17.8 [11.6-27.4])] and also substituted for the potent cannabinoid receptor agonist CP55,940 [2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol] in the drug-discrimination paradigm [ED50 (95% CL) values in mg/kg: MJN110 (0.84 [0.69-1.02]) > JZL184 (24.9 [14.6-42.5])]; however, these compounds elicited differential effects on locomotor behavior. Similar to cannabinoid 1 (CB1) receptor agonists, JZL184 produced hypomotility, whereas MJN110 increased locomotor behavior and did not produce catalepsy or hypothermia. Although both drugs substituted for CP55,940 in the drug discrimination assay, MJN110 was more potent in reversing allodynia in the CCI model than in producing CP55,940-like effects. Overall, these results suggest that MAGL inhibition may alleviate neuropathic pain, while displaying limited cannabimimetic effects compared with direct CB1 receptor agonists., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)
- Published
- 2015
- Full Text
- View/download PDF
17. High on food: the interaction between the neural circuits for feeding and for reward.
- Author
-
Liu JJ, Mukherjee D, Haritan D, Ignatowska-Jankowska B, Liu J, Citri A, and Pang ZP
- Abstract
Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.
- Published
- 2015
- Full Text
- View/download PDF
18. Prolonged monoacylglycerol lipase blockade causes equivalent cannabinoid receptor type 1 receptor-mediated adaptations in fatty acid amide hydrolase wild-type and knockout mice.
- Author
-
Schlosburg JE, Kinsey SG, Ignatowska-Jankowska B, Ramesh D, Abdullah RA, Tao Q, Booker L, Long JZ, Selley DE, Cravatt BF, and Lichtman AH
- Subjects
- Adaptation, Physiological, Animals, Dronabinol pharmacology, Endocannabinoids analysis, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Amidohydrolases physiology, Benzodioxoles pharmacology, Monoacylglycerol Lipases antagonists & inhibitors, Piperidines pharmacology, Receptor, Cannabinoid, CB1 physiology
- Abstract
Complementary genetic and pharmacological approaches to inhibit monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), the primary hydrolytic enzymes of the respective endogenous cannabinoids 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine, enable the exploration of potential therapeutic applications and physiologic roles of these enzymes. Complete and simultaneous inhibition of both FAAH and MAGL produces greatly enhanced cannabimimetic responses, including increased antinociception, and other cannabimimetic effects, far beyond those seen with inhibition of either enzyme alone. While cannabinoid receptor type 1 (CB1) function is maintained following chronic FAAH inactivation, prolonged excessive elevation of brain 2-AG levels, via MAGL inhibition, elicits both behavioral and molecular signs of cannabinoid tolerance and dependence. Here, we evaluated the consequences of a high dose of the MAGL inhibitor JZL184 [4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate; 40 mg/kg] given acutely or for 6 days in FAAH(-/-) and (+/+) mice. While acute administration of JZL184 to FAAH(-/-) mice enhanced the magnitude of a subset of cannabimimetic responses, repeated JZL184 treatment led to tolerance to its antinociceptive effects, cross-tolerance to the pharmacological effects of Δ(9)-tetrahydrocannabinol, decreases in CB1 receptor agonist-stimulated guanosine 5'-O-(3-[(35)S]thio)triphosphate binding, and dependence as indicated by rimonabant-precipitated withdrawal behaviors, regardless of genotype. Together, these data suggest that simultaneous elevation of both endocannabinoids elicits enhanced cannabimimetic activity but MAGL inhibition drives CB1 receptor functional tolerance and cannabinoid dependence., (Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.)
- Published
- 2014
- Full Text
- View/download PDF
19. Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors.
- Author
-
Ignatowska-Jankowska B, Jankowski MM, and Swiergiel AH
- Subjects
- Animals, Dose-Response Relationship, Drug, Indoles pharmacology, Male, Rats, Rats, Wistar, Receptor, Cannabinoid, CB2 antagonists & inhibitors, Time Factors, Body Weight drug effects, Cannabidiol pharmacology, Receptor, Cannabinoid, CB2 metabolism
- Abstract
Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis sativa, with well recognized therapeutic potential. Considering the importance of the endogenous cannabinoid system to the regulation of food intake and energy balance we studied the effects of repeated CBD administration on body weight gains in rats. Male Wistar rats (260 ± 20 g at start of study) received intraperitoneal injections of CBD at doses of 2.5 and 5mg/kg/day for 14 consecutive days and body weight gains were monitored. Both doses of CBD produced significant decrease in body weight gain, with the effect produced by 5mg/kg being more pronounced. The CB2 receptor selective antagonist, AM630, blocked the decrease in body weight gain. AM630 alone did not affect body weight gain. The results suggest that CBD has the ability to alter body weight gain, possibly via the CB2 receptor. CB2 receptors may play a role in the regulation of body weight and the effects of CB2 specific ligands should be further investigated in studies of body weight regulation., (© 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
20. Cocaine administration increases CD4/CD8 lymphocyte ratio in peripheral blood despite lymphopenia and elevated corticosterone.
- Author
-
Jankowski MM, Ignatowska-Jankowska B, Glac W, and Swiergiel AH
- Subjects
- Animals, Corticosterone metabolism, Drug Administration Schedule, Interferon-gamma, Male, Rats, Rats, Wistar, Weight Gain drug effects, CD4-CD8 Ratio, Cocaine pharmacology, Corticosterone blood, Lymphopenia metabolism, T-Lymphocytes drug effects
- Abstract
The CD4/CD8 lymphocyte ratio in peripheral blood is used in the diagnosis of HIV infection, autoimmune disorders or susceptibility to infections. The present experiment aimed to evaluate the lymphocyte subsets, their distribution and CD4/CD8 ratio in blood after repeated, intravenous administration of cocaine. Adult male Wistar rats received three daily, in 30 min intervals, intravenous infusions of cocaine hydrochloride (5 mg/kg) or saline for 14 consecutive days. After each infusion the locomotor-activating effects of cocaine were assessed. Blood samples were collected 30 min after the last daily infusion on the 1st, 7th and 14th day of treatment. Total leukocyte numbers, percentages of leukocyte subpopulations, and T, B, NK, T CD4+, and T CD8+ lymphocyte subsets, IFN-γ, and plasma corticosterone were determined. Repeated cocaine treatment resulted in an increase in neutrophil numbers and a significant decrease in total leukocyte and lymphocyte numbers involving a significant reduction in numbers of T, B, and NK lymphocyte subsets. T CD4+ and T CD8+ lymphocyte numbers were reduced but with a considerably smaller decrease in T CD4+ number. Cocaine treatment altered proportions between the lymphocyte subsets by decreasing the percentages of T CD8+, B, and NK cells but increasing a percentage of T CD4+ cells. Destabilization in proportions between T CD4+ and T CD8+ was manifested as an elevated CD4/CD8 ratio that occurred despite increased plasma corticosterone and the lymphocytopenia. Cocaine did not affect the concentration of IFN-γ. The results suggest that although cocaine induced lymphopenia, it did not suppress the overall immune activity in terms of the CD4/CD8 ratio., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
21. Cannabidiol-induced lymphopenia does not involve NKT and NK cells.
- Author
-
Ignatowska-Jankowska B, Jankowski M, Glac W, and Swiergel AH
- Subjects
- Animals, Cannabidiol pharmacology, Dose-Response Relationship, Drug, Immunologic Factors pharmacology, Lymphocyte Subsets cytology, Lymphopenia immunology, Male, Rats, Cannabidiol immunology, Immunologic Factors immunology, Killer Cells, Natural drug effects, Lymphocyte Subsets drug effects, Lymphopenia chemically induced, Natural Killer T-Cells drug effects
- Abstract
The major non-psychoactive compound of cannabis plant, cannabidiol, has been reported to be a promising therapeutic agent for many inflammatory, autoimmune and neurodegenerative diseases. In spite of growing interest in therapeutic use of cannabidiol very little is known about its influence on the immune system. Present study aimed to evaluate lymphocyte subsets distribution in peripheral blood after repeated, systemic administration of cannabidiol. Adult male Wistar rats received intraperitoneal injections of vehicle or cannabidiol at dose of 2.5 or 5 mg/kg/day, for 14 consecutive days. Blood samples were collected one hour after the last injection. Three-color immunofluorescent antibody staining procedure (CD3-FITC/CD45RA-PC7/CD161A-APC and CD3-FITC/CD4-PC7/CD8-APC) was used for determination of T, B, NK, NKT, T helper, and T cytotoxic lymphocyte subsets. Total leukocyte number and percentage numbers of leukocyte subpopulations were also assessed. Administration of cannabidiol at dose of 5 mg/kg caused a significant decrease in total leukocyte number and a significant fall in total numbers of T, B, and both T helper and T cytotoxic lymphocyte subsets. This immunosuppressive effect did not affect the total numbers of NK and NKT cells that are responsible for the primary, nonspecific antiviral and antitumor immune response. In contrast, administration of cannabidiol at dose of 2.5 mg/kg increased the total and percentage NKT cells numbers, and the percentage number of NK cells. The results suggest that repeated treatment with cannabidiol inhibits specific immunity by reduction of T, B, T cytotoxic, and T helper cell numbers, and may enhance nonspecific antiviral and antitumor immune response related to NK and NKT cells.
- Published
- 2009
22. Damage to the nucleus accumbens shell but not core impairs ventral tegmental area stimulation-induced feeding.
- Author
-
Trojniar W, Plucińska K, Ignatowska-Jankowska B, and Jankowski M
- Subjects
- Animals, Eating, Electric Stimulation, Male, Motor Activity physiology, Rats, Rats, Wistar, Feeding Behavior physiology, Motivation, Nucleus Accumbens physiology, Ventral Tegmental Area physiology
- Abstract
Food intake is regulated not only by homeostatic requirements but also by emotional factors (e.g. palatability of food, alleviation of emotional tension etc.). The nucleus accumbens (Acb) is a part of the mesolimbic dopaminergic system which is responsible for a positive emotional aspect of various homeostasis-relevant stimuli. In the present work, we tested the Acb involvement in feeding behaviour using an experimental paradigm specifically designed to assess motivational vs motor aspect of food ingestion. In rats, feeding was evoked by electrical stimulation of the midbrain ventral tegmental area (a somatodendritic region of mesolimbic system) and assessed quantitatively with the use of the latency to feed/stimulation frequency curve-shift paradigm before and after electrolytic lesion of Acb. An impairment of stimulation-induced feeding manifesting as an elevation of the reaction threshold and a rightward, parallel shift of the stimulation frequency/reaction latency curve in the range of frequency which is sensitive to motivational aspects of food occurred after lesions localized mainly in the Acb shell. The lesions situated mainly in the Acb core were ineffective. The results obtained indicate that the Acb shell connected with the limbic system but not the motor-related Acb core affects motivational aspects of feeding behaviour.
- Published
- 2007
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.