16 results on '"Kekesi, Gabriella"'
Search Results
2. The antinociceptive interaction of anandamide and adenosine at the spinal level
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Tuboly, Gabor, Kekesi, Gabriella, Nagy, Edit, Benedek, György, and Horvath, Gyöngyi
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ADENOSINES , *PHYSIOLOGICAL effects of caffeine , *LABORATORY rats , *HYPERALGESIA treatment , *LIGANDS (Biochemistry) , *SENSORY receptors - Abstract
Abstract: Both anandamide and adenosine have significant roles in pain mechanisms, but no data are available concerning their interaction at the spinal level. The goal of this study was to determine how adenosine and the adenosine receptor antagonist caffeine affect the antinociceptive effect of anandamide. The pain sensitivity was assessed by the acute tail-flick test and by paw withdrawal test after carrageenan-induced inflammation. The substances were administered intrathecally to male Wistar rats. Anandamide alone (1, 30 and 100 μg) dose-dependently decreased the hyperalgesia, however it had low potency in the tail-flick test. Neither adenosine (100 μg) nor caffeine (400 μg) alone changed the pain sensitivity markedly. Their combination caused a short-lasting antihyperalgesia, but it did not influence the tail-flick latency. Both adenosine and caffeine decreased the antihyperalgesic potential of 100 μg anandamide, while adenosine–caffeine pretreatment temporarily enhanced its effect. As regards acute heat pain sensitivity, no combination with anandamide influenced the effect of anandamide. These findings provide new data concerning the interaction between two endogenous ligands and caffeine. Since these substances may exert effects on several receptors and/or systems, their interaction in vivo must be very complex and the net outcome after their coadministration could not been predicted from the in vitro results. [Copyright &y& Elsevier]
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- 2009
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3. Antinociceptive interactions of triple and quadruple combinations of endogenous ligands at the spinal level
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Horvath, Gyongyi, Kekesi, Gabriella, Tuboly, Gabor, and Benedek, Gyorgy
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ADENOSINES , *ADENINE , *DRUG interactions , *DRUG side effects - Abstract
Abstract: A very interesting and rapidly developing field of pain research is related to the roles of different endogenous ligands. This study determined the antinociceptive interactions of triple and quadruple combinations of different endogenous ligands (endomorphin-1, adenosine, agmatine and kynurenic acid) on carrageenan-induced inflammatory pain model at the spinal level. Intrathecal infusion (60 min) of these drugs alone, in double, triple or quadruple combinations, was followed by a 60-min observation period. During the infusion, antihyperalgesic effect of 0.3 μg/min endomorphin-1 was higher in the triple combinations than those in the double combinations. After cessation of drug administration, only the combination of 0.3 μg/min endomorphin-1, 1 μg/min agmatine, and 0.3 μg/min adenosine was more effective than the double combinations. In quadruple combinations, the antinociceptive effects of both 0.1 and 0.3 μg/min endomorphin-1 were significantly potentiated by the otherwise ineffective triple combination of adenosine, agmatine, and kynurenic acid. No side effects could be observed at these doses. These results demonstrate that triple and quadruple combinations of these endogenous ligands caused more effective antihyperalgesia compared with double combinations. Accordingly, the doses of these substances could be further reduced, thus, reinforcing the view that complex activation and/or inhibition of different systems can be sufficiently effective in blocking nociception without adverse effects. Because all of these drugs had effects on various receptors and systems, the possible types of these interactions were discussed. [Copyright &y& Elsevier]
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- 2007
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4. Interaction of endogenous ligands mediating antinociception
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Horvath, Gyongyi and Kekesi, Gabriella
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NEURAL transmission , *NEURAL circuitry , *NEUROPHYSIOLOGY , *ENDOCRINE glands - Abstract
Abstract: It is well known that a multitude of transmitters and receptors are involved in the nociceptive system, some of them increasing and others inhibiting the pain sensation both peripherally and centrally. These substances, which include neurotransmitters, hormones, etc., can modify the activity of nerves involved in the pain pathways. Furthermore, the organism itself can express very effective antinociception under different circumstances (e.g. stress), and, during such situations, the levels of various endogenous ligands change. A very exciting field of pain research relates to the roles of endogenous ligands. Most of them have been suggested to influence pain transmission, but only a few studies have been performed on the interactions of different endogenous ligands. This review focuses on the results of antinociceptive interactions after the co-administration of endogenous ligands. The data based on 55 situations reveal that the interactions between the endogenous ligands are very different, depending on the substances, the pain tests, the species of animals and the route of administrations. It is also revealed that only a few of the possible interactions between endogenous ligands have been investigated to date, in spite of the fact that the type of antinociceptive interaction between different endogenous ligands could hardly be predicted. The results indicate that the combination of endogenous ligands should not be omitted from the pain therapy arsenal. Attention will hopefully be drawn to the complex interdependence of endogenous ligands and their potential use in clinical practice. [Copyright &y& Elsevier]
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- 2006
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5. Dose-independent antinociceptive interaction of endogenous ligands at the spinal level
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Kekesi, Gabriella, Joo, Gabriella, Csullog, Emese, Peter-Szabo, Mihaly, Benedek, Gyorgy, and Horvath, Gyongyi
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PAIN , *LIGANDS (Biochemistry) , *SPINAL cord , *RATS - Abstract
Adenosine, agmatine and kynurenic acid are endogenous ligands acting on different (e.g. adenosine, NMDA, α2-adrenergic and imidazoline) receptors with a potential role in nociception at the spinal level. Their antinociceptive effects have already been investigated as monotherapy, but only a few studies have reported on their effects on the potency of other drugs. The purpose of the present study was carried out to analyse their interactions during continuous intrathecal co-administration in a carrageenan-induced thermal hyperalgesia model in rats. A paw withdrawal test was used for nociceptive testing. The intrathecal infusion (60 min) of these three drugs was administered alone or in combinations (kynurenic acid+adenosine or agmatine; adenosine+agmatine), which was followed by an additional 60-min observation period. Kynurenic acid alone was ineffective, while adenosine and agmatine alone caused a slight increase in pain threshold. However, independently of the applied doses all of the combinations significantly (p<0.05) increased the paw withdrawal latencies on the inflamed side during and after the infusion, but were almost ineffective on the normal side. The adenosine+kynurenic acid combination was the most effective: namely, that it relieved thermal hyperalgesia in all the applied dose combinations. Treatment with the kynurenic acid-containing combinations also caused dose-dependent side-effects (motor impairment and excitation), despite the fact that monotherapy with kynurenic acid in the applied dose (0.1 μg/min) did not result in adverse effects. [Copyright &y& Elsevier]
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- 2004
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6. The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats
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Kekesi, Gabriella, Joo, Gabriella, Csullog, Emese, Dobos, Ildiko, Klimscha, Walter, Toth, Kalman, Benedek, György, and Horvath, Gyöngyi
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CHEMICAL inhibitors , *OPIOIDS - Abstract
Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-d-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous μ-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1–4 μg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01–0.1 μg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1–1 μg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects. [Copyright &y& Elsevier]
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- 2002
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7. Cognitive training improves the disturbed behavioral architecture of schizophrenia-like rats, "Wisket".
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Horvath, Gyongyi, Liszli, Peter, Kekesi, Gabriella, Büki, Alexandra, and Benedek, Gyorgy
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COGNITIVE training , *BEHAVIOR therapy , *PREDICTIVE validity , *PEOPLE with schizophrenia - Abstract
Abstract Translational schizophrenia research depends on the relevance of animal models supported by reliable tests. Human data suggest that the intensive cognitive training in schizophrenia improves the memory impairments and decreases the chance of acute psychiatric remission. Here we examined the effects of a 10-day long training session in the behavioral architecture of a new schizophrenia-like rat substrain (Wisket) in a narrow square corridor with food rewards (AMBITUS). The instrument was designed to model the natural environment of rats and enable the simultaneous recording of multiple behavioral parameters. For the compact visualization of differences between the Wisket and control animals in several parameters (behavioromics), color-coded grid plots were applied. The Wisket animals exhibited an altered pattern and/or amount of locomotion, exploratory and food collecting activity at the first few days, revealing impaired motivation, attention, anxiety and learning ability (face validity). Most of the parameters normalized with training, except for the decreased exploratory activity. This resembles the effects of cognitive behavioral therapy in human schizophrenics providing a significant support for the predictive validity of this substrain as an animal model of schizophrenia. This study also highlights the importance of behavior tests that investigate the egocentric learning ability during reward-based tasks. Highlights • A complex animal model of schizophrenia led to altered behavioral architecture. • The Wisket animals exhibited impaired motivation, attention and anxiety. • Most of the parameters normalized with training, except for exploratory activity. • Color-coded figures might be useful approaches for behavioral characterization. • Cognitive training in AMBITUS resulted long-term cognitive improvement. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Impaired pupillary control in “schizophrenia-like” WISKET rats.
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Büki, Alexandra, Kalmár, György, Kekesi, Gabriella, Benedek, Gyorgy, Nyúl, László G., and Horvath, Gyongyi
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PEOPLE with schizophrenia , *REFLEXES , *MALES , *EDUCATIONAL films , *LABORATORY rats , *DISEASES - Abstract
Patients with schizophrenia show impairments in autonomic regulation, including pupillomotor control. The aim of this study was to explore the changes of pupillary light reflex in a new substrain (WISKET) with several schizophrenia-like alterations. Male WISKET rats housed individually (for four weeks) and treated with ketamine (for 3 × 5 days) after weaning and naive group-housed Wistar rats (controls) were involved in the study. The pupillary light reflex was studied in two series after sedation (diazepam) or anesthesia (chloral hydrate). Video recordings were evaluated with custom made video analyzer software. Several significant changes were observed between the two groups: the initial and minimum pupil diameters were greater, the degree of the constriction was lower, and the flatness of the curve and the total duration of constriction were shorter in the sedated WISKET rats. No other pupillary parameters (latency, amplitude and redilation) showed significant alterations. Chloral hydrate anesthesia prolonged the constriction and redilation processes compared to the sedated animals, and diminished the differences between the groups. In conclusion, WISKET rats showed disturbances in the pupillary light reflex, suggesting a general shift of autonomic balance towards a sympathetic predominance. The results provide further evidence to support the validity of WISKET rats as a complex, chronic animal model of schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2018
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9. Electrophysiological alterations in a complex rat model of schizophrenia.
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Horvath, Gyongyi, Petrovszki, Zita, Kekesi, Gabriella, Tuboly, Gabor, Bodosi, Balazs, Horvath, Janos, Gombkötő, Peter, Benedek, Gyorgy, and Nagy, Attila
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ELECTROPHYSIOLOGY , *SCHIZOPHRENIA treatment , *AUDITORY evoked response , *SOCIAL isolation , *NEUROPHYSIOLOGY , *LABORATORY rats - Abstract
Background Psychiatric disorders are frequently accompanied by changes in brain electrical oscillations and abnormal auditory event related potentials. The goal of this study was to characterize these parameters of a new rat substrain showing several alterations related to schizophrenia. Methods Male rats of the new substrain, developed by selective breeding after combined subchronic ketamine treatment and postweaning social isolation, and naive Wistar ones group-housed without any interventions were involved in the present study. At the age of 3 months, animals were implanted with cortical electroencephalography electrodes. Auditory evoked potentials during paired-click stimuli and power of oscillation in different frequency bands were determined with and without acute ketamine (20 mg/kg) treatment. Results Regarding the auditory evoked potentials, the latency of P2 was delayed and the amplitude of N1 peak was lower in the new substrain. The new substrain showed increased power of oscillations in the theta, alpha and beta bands, while decreased power was detected in delta and gamma2 bands (52–70 Hz) compared with control animals. Acute ketamine treatment increased the gamma1 band (30–48 Hz) power in both groups, while it elicited significant changes only in the new substrain in the total power and in alpha, beta and gamma2 bands. Conclusions The validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia. [ABSTRACT FROM AUTHOR]
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- 2016
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10. In vivo potency of different ligands on voltage-gated sodium channels.
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Safrany-Fark, Arpad, Petrovszki, Zita, Kekesi, Gabriella, Liszli, Peter, Benedek, Gyorgy, Keresztes, Csilla, and Horvath, Gyongyi
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SODIUM channels , *ELECTRIC potential , *LIGANDS (Biochemistry) , *ION channels , *POTENTIAL energy - Abstract
The Ranvier nodes of thick myelinated nerve fibers contain almost exclusively voltage-gated sodium channels (Na v s), while the unmyelinated fibers have several receptors (e.g., cannabinoid, transient receptor potential vanilloid receptor 1), too. Therefore, a nerve which contains only motor fibers can be an appropriate in vivo model for selective influence of Na v s. The goals were to evaluate the potency of local anesthetic drugs on such a nerve in vivo; furthermore, to investigate the effects of ligands with different structures (arachidonic acid, anandamide, capsaicin and nisoxetine) that were proved to inhibit Na v s in vitro with antinociceptive properties. The marginal mandibular branch of the facial nerve was explored in anesthetized Wistar rats; after its stimulation, the electrical activity of the vibrissae muscles was registered following the perineural injection of different drugs. Lidocaine, bupivacaine and ropivacaine evoked dose-dependent decrease in electromyographic activity, i.e., lidocaine had lower potency than bupivacaine or ropivacaine. QX-314 did not cause any effect by itself, but its co-application with lidocaine produced a prolonged inhibition. Nisoxetine had a very low potency. While anandamide and capsaicin in high doses caused about 50% decrease in the amplitude of action potential, arachidonic acid did not influence the responses. We proved that the classical local anesthetics have high potency on motor nerves, suggesting that this method might be a reliable model for selective targeting of Navs in vivo circumstances. It is proposed that the effects of these endogenous lipids and capsaicin on sensory fibers are not primarily mediated by Navs. [ABSTRACT FROM AUTHOR]
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- 2015
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11. The effects of juvenile capsaicin desensitization in rats: Behavioral impairments.
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Petrovszki, Zita, Adam, Gábor, Kekesi, Gabriella, Tuboly, Gábor, Morvay, Zita, Nagy, Endre, Benedek, György, and Horvath, Gyöngyi
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CAPSAICIN , *DESENSITIZATION (Psychotherapy) , *ENCEPHALITIS , *BODY temperature regulation , *SCHIZOPHRENIA , *LABORATORY rats , *ANIMAL behavior - Abstract
Abstract: Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22°C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia. [Copyright &y& Elsevier]
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- 2014
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12. Wisket rat model of schizophrenia: Impaired motivation and, altered brain structure, but no anhedonia.
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Büki, Alexandra, Bohár, Zsuzsanna, Kekesi, Gabriella, Vécsei, László, and Horvath, Gyongyi
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BRAIN anatomy , *ANHEDONIA , *ANIMAL disease models , *SCHIZOPHRENIA , *COGNITION disorders - Abstract
• Hedonic behavior and brain structure were studied in a three-hit schizophrenia model. • Schizophrenia-like Wisket rats have cognitive dysfunction without anhedonia. • Anhedonic behavior is not involved in the impaired motivation of Wisket rats. • Wisket rats have similar structural changes in the brain as in schizophrenia. It is well-known that the poor cognition in schizophrenia is strongly linked to negative symptoms, including motivational deficit, which due to, at least partially, anhedonia. The goal of this study was to explore whether the schizophrenia-like Wisket animals with impaired motivation (obtained in the reward-based hole-board test), also show decreased hedonic behavior (investigated with the sucrose preference test). While neurochemical alterations of different neurotransmitter systems have been detected in the Wisket rats, no research has been performed on structural changes. Therefore, our additional aim was to reveal potential neuroanatomical and structural alterations in different brain regions in these rats. The rats showed decreased general motor activity (locomotion, rearing and exploration) and impaired task performance in the hole-board test compared to the controls, whereas no significant difference was observed in the sucrose preference test between the groups. The Wisket rats exhibited a significant decrease in the frontal cortical thickness and the hippocampal area, and moderate increases in the lateral ventricles and cell disarray in the CA3 subfield of hippocampus. To our knowledge, this is the first study to investigate the hedonic behavior and neuroanatomical alterations in a multi-hit animal model of schizophrenia. The results obtained in the sucrose preference test suggest that anhedonic behavior might not be involved in the impaired motivation obtained in the hole-board test. The neuropathological changes agree with findings obtained in patients with schizophrenia, which refine the high face validity of the Wisket model. [ABSTRACT FROM AUTHOR]
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- 2022
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13. The inimitable kynurenic acid: The roles of different ionotropic receptors in the action of kynurenic acid at a spinal level.
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Tuboly, Gabor, Tar, Lilla, Bohar, Zsuzsanna, Safrany-Fark, Arpad, Petrovszki, Zita, Kekesi, Gabriella, Vecsei, Laszlo, Pardutz, Arpad, and Horvath, Gyongyi
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HYDROXYQUINOLINE , *NICOTINIC receptors , *NEURAL circuitry , *OSTEOARTHRITIS , *LABORATORY rats , *METHYL aspartate receptors , *PHENCYCLIDINE - Abstract
Kynurenic acid (KYNA) is a neuroactive metabolite that interacts with NMDA, AMPA/kainate and alpha 7 nicotinic receptors. The goal of this study was to clarify the roles of these receptors in the action of KYNA at a spinal level by using highly specific receptor antagonists alone or in triple combinations. Chronic osteoarthritis-like joint pain was induced with monosodium-iodoacetate in male Wistar rats. Mechanical allodynia and motor function were quantified. In the first series we determined the dose–response and time course effects of intrathecally administered KYNA (10–100 μg), d -(−)-2-amino-5-phosphonopentanoic acid (AP5; an NMDA receptor antagonist; 10–200 μg), methyllycaconitine (MLA; an alpha 7 nicotinic receptor antagonist; 100–200 μg) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzoquinoxaline-7-sulfonamide (NBQX; an AMPA/kainate receptor antagonist; 1–20 μg). In the second series, four different triple combinations of MLA, AP5 and NBQX were investigated. Intrathecal administration of KYNA caused a dose-dependent motor impairment and antinociception. The highly specific NMDA receptor antagonist AP5 caused a motor impairment and antinociception with lower potency. High doses of NBQX resulted in significant antinociception with a slight motor impairment, while only the highest dose of MLA gave rise to significant antinociception with a slight motor impairment. After the coadministration of these ligands as combinations, no potentiation was observed. It may be supposed that the effects of KYNA are primarily due to the inhibition of NMDA receptors at both glycine and phencyclidine (PCP) binding sites, and not to the interactions at the different ionotropic receptors, but the mechanisms behind its high bio-efficiency are still unknown. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Characterization of gene–environment interactions by behavioral profiling of selectively bred rats: The effect of NMDA receptor inhibition and social isolation
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Petrovszki, Zita, Adam, Gabor, Tuboly, Gabor, Kekesi, Gabriella, Benedek, Gyorgy, Keri, Szabolcs, and Horvath, Gyongyi
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NEUROBEHAVIORAL disorders , *LABORATORY rats , *METHYL aspartate receptors , *SOCIAL isolation , *SCHIZOPHRENIA , *INFANT weaning - Abstract
Abstract: Gene–environment interactions have an important role in the development of psychiatric disorders. To generate and validate a new substrain of rats with signs related to schizophrenia, we used selective breeding after postweaning social isolation and chronic ketamine treatment through several generations of animals and compared the subsequent strain to naive rats that were not genetically manipulated. We further investigated whether social isolation and ketamine treatment augmented the appearance of schizophrenic-like signs in these rats. Four experimental groups were studied (n =6–15 rats/group): naive rats without any treatment (NaNo); naive rats with postweaning social isolation and ketamine treatment (NaTr); 15th generation of selectively bred animals without any treatment (SelNo) or selectively bred rats with both isolation and ketamine treatment (SelTr). The startle reaction, tail-flick and novel object recognition tests were used to classify the animals into low- or high-risk for schizophrenia. Reduced pain sensitivity, higher degree of the startle reaction, disturbed prepulse inhibition, altered motor activity and decreased differentiation index in the memory test were observed in the 15th generation of the substrain, along with enhanced grooming behavior. Five functional indices (TF latency, startle reaction, prepulse inhibition, differentiation index, and grooming activity) were rated from 0 to 2, and the analysis of the summarized score revealed that the NaNo group had the lowest overall indication of schizophrenic-like signs, while the SelTr animals scored the highest, suggesting that both heritable and environmental factors were important in the generation of the behavioral alterations. We assume that further breeding after this complex treatment may lead to a valid and reliable animal model of schizophrenia. [Copyright &y& Elsevier]
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- 2013
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15. Characterization of dopamine D2 receptor binding, expression and signaling in different brain regions of control and schizophrenia-model Wisket rats.
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Szűcs, Edina, Ducza, Eszter, Büki, Alexandra, Kekesi, Gabriella, Benyhe, Sándor, and Horvath, Gyöngyi
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DOPAMINE receptors , *CEREBRAL cortex , *BINDING site assay , *OLFACTORY bulb , *SCHIZOPHRENIA , *ANIMAL disease models - Abstract
• Stimulation of D 2 R caused enhanced G-protein activation in several brain sites of Wisket animals. • Maximal binding capacity of D 2 Rs increased in the model animals. • D 2 R mRNA expression showed a trend for the increase in brain areas of Wisket animals. • D 2 R protein expression increased in the hippocampus and the PFC in Wisket rats. • Schizophrenia-like Wisket animals show altered D 2 receptor expression and function. In previous studies we have shown that a three-hit animal model of schizophrenia (Wisket rat) has several behavioral impairments related to the disorder along with altered mu-opioid (MOP) and cannabinoid (CB1) receptor signaling. As the dopamine hypothesis of schizophrenia is central to research in the field, the goal of the present study was to investigate dopaminergic D 2 receptor (D 2 R) functions (binding capacity, G-protein activation and expression) in several brain regions (hippocampus, prefrontal cortex, striatum, olfactory bulb, cerebellum, brainstem, cortex and diencephalon) of control (Wistar) and Wisket rats. It was found that the D 2 R mediated maximal activation of G-proteins was substantially higher in hippocampus, striatum and olfactory bulb membranes prepared from the Wisket than in control animals, which was accompanied with lower potency of the D 2 R-mediated G-protein activation. In contrast, enhanced potency was detected in the prefrontal cortex without changes in the maximal activation. In saturation binding assays the maximal binding capacity of D 2 Rs was higher in the model animals in cerebral cortex, striatum and lower in the brainstem, while no changes in the dissociation constant values were detected. The D 2 R mRNA expression showed a trend for greater level in the investigated areas, while the D 2 R protein expression was significantly higher of Wisket rats compared to Wistar animals in the hippocampus and in the prefrontal cortex but not in the cerebellum. This study proved that the Wisket animals show altered D 2 receptor expression and function which might be related to the schizophrenia-like symptoms. [ABSTRACT FROM AUTHOR]
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- 2020
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16. Distinct changes in chronic pain sensitivity and oxytocin receptor expression in a new rat model (Wisket) of schizophrenia.
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Banki, László, Büki, Alexandra, Horvath, Gyongyi, Kekesi, Gabriella, Kis, Gyongyi, Somogyvári, Ferenc, Jancsó, Gábor, Vécsei, Lászlo, Varga, Endre, and Tuboly, Gabor
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OXYTOCIN receptors , *CHRONIC pain , *CANNABINOID receptors , *OLFACTORY bulb , *OPIOID receptors - Abstract
• Schizophrenia-like animals (Wisket) displayed decreased chronic pain sensitivity. • The opioid ligands preserved their antinociceptive effects in the Wisket animals. • The Wisket animals had impaired oxytocin gene expression in several brain areas. • Impaired antinociceptive systems are not inevitably matched with hyperalgesia. Clinical studies have shown that schizophrenia is accompanied by hypoalgesia. Accordingly, we have previously reported that a chronic schizophrenia-related rat substrain (Wisket) showed decreased acute heat pain sensitivity. The aim of the present study was to determine the mechanical pain sensitivity and the effects of opioid ligands in a chronic osteoarthritic pain model generated using Wisket rats. Our previous molecular biological studies indicated that the impairment in opioid and cannabinoid receptor functions observed in these animals did not explain their altered pain sensitivity. Therefore, we aimed to investigate another endogenous antinociceptive system, i.e., the oxytocinergic system (which is also implicated in schizophrenia) via the determination the brain-region specific oxytocin receptor mRNA expression in Wisket rats. Osteoarthritis was induced in male adult control Wistar rats without any interventions and in Wisket rats after juvenile social isolation and ketamine treatment. The degree of allodynia and the effects of systemic morphine or intrathecal endomorphin-1 administration were determined. Furthermore, the expression of the oxytocin receptor mRNA was assessed in different brain structures (prefrontal cortex, striatum, diencephalon, brainstem, and olfactory bulb). A lower degree of allodynia was observed in the Wisket group compared with control animals 1 and 2 weeks after the induction of osteoarthritis, which was accompanied by a comparable degree of edema. Systemically or intrathecally applied opioids caused similar time-response curves in both groups, with apparently shorter effects in Wisket animals. The expression of the oxytocin receptor mRNA was lower in most of the brain regions (with the exception of the diencephalon) investigated in Wisket rats vs. the control animals. In summary, both acute and chronic hypoalgesia (as nonspecific symptoms in patients with schizophrenia) can be simulated in Wisket animals as endophenotypes despite the impairment of the endogenous antinociceptive systems evaluated. Thus, this model might be an appropriate tool for further investigation of the molecular basis of altered pain perception in schizophrenia. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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