PT603. The contribution of resveratrol to the antiepileptic effects of diazepam and gabapentin

s | 21 Conclusions: Oleoylethanolamide modulates motivation of intra-gastric feeding, possibly through normalization of PPAR-αdependent vagal feedback to the brain in rodents. This supports its homeostatic function for regulating dietary fat intake via vagal-nigro-striatal pathways. Our study suggests that oleoylethanolamide mediates reward-associated neural processes and this signaling plays an important role for hedonic regulation of food-craving and obesity in humans. It may be a valuable target for developing novel antiobesity drugs. EPILEPSY: PT601 – PT608 PT601 Evaluation of the behavioral and physiological roles of BRINP family genes in epileptic kindled mice Evaluation of the behavioral and physiological roles of BRINP family genes in epileptic kindled mice Hiroaki Araki1), Kenshi Takechi1), Yasuhiro Kono2), Akihiro Tanaka1), Miwako Kobayashi2), Ichiro Matsuoka2) 1) Division of Pharmacy, Ehime University Hospital, 1-1-1 Toon, Ehime 791-0295, Japan 2) Department of Physiological Chemistry, Coll. of Pharm. Sci. Matsuyama Universsity, 4-2 Bunkyo-cho, Matsuyama, Ehime 790–8578, Japan Abstract Objective: Induction of the BMP/RA-induced neural specific protein-1 (BRINP1) gene begins in the mouse nervous system from the early developmental stages, and it is highly expressed in various brain regions in adulthood. Studies have demonstrated that epileptic patients tend to have comorbid similar psychiatric symptoms to attention deficient hyperactivity disorder and autistic patients. In this study, the physiological role of BRINP1 was evaluated by conducting behavioral pharmacological tests in kindled BRINP1-deficient (KO) mice. Using immunohistochemistry, c-Fos expression levels in kindled mice were also studied. Methods: To induce kindling, mice were intraperitoneally injected with pentylenetetrazol at a dose of 35 mg/kg once every 48 h. After the final challenge, mice were tested. Results: The development of kindled convulsions was not significantly different between wild-type and BRINP1-KO mice. BRINP1-KO mice showed less anxiety-like behavior than wildtype mice and the induction of kindling reduced anxiety-likeObjective: Induction of the BMP/RA-induced neural specific protein-1 (BRINP1) gene begins in the mouse nervous system from the early developmental stages, and it is highly expressed in various brain regions in adulthood. Studies have demonstrated that epileptic patients tend to have comorbid similar psychiatric symptoms to attention deficient hyperactivity disorder and autistic patients. In this study, the physiological role of BRINP1 was evaluated by conducting behavioral pharmacological tests in kindled BRINP1-deficient (KO) mice. Using immunohistochemistry, c-Fos expression levels in kindled mice were also studied. Methods: To induce kindling, mice were intraperitoneally injected with pentylenetetrazol at a dose of 35 mg/kg once every 48 h. After the final challenge, mice were tested. Results: The development of kindled convulsions was not significantly different between wild-type and BRINP1-KO mice. BRINP1-KO mice showed less anxiety-like behavior than wildtype mice and the induction of kindling reduced anxiety-like behavior in both genotypes in the elevated plus maze test. In addition, c-Fos expression at steady state was significantly increased in the dentate gyrus of KO-kindled mice compared with wild-type mice. Furthermore, c-Fos expression was increased in the hippocampus, amygdala, and hypothalamus in both kindled and KO-kindled mice at 3 hours after pentylenetetrazol injection, although this increase was similar in KO and wild-type mice. Conclusion: These findings suggest that the BRINP1 gene is not directly involved in the epileptic behavior of kindling convulsions. However, elevated c-Fos expression in dentate granule neurons in BRINP1-KO mice at steady state implicated that BRINP1 involves regulation of neuronal excitability which is responsible for preventing onset of behavioral psychiatric symptoms. PT602 The role of nitric oxide on the anticonvulsant activity of agmatine, valproic acid, gabapentin and phenytoin in mice Bilgin Kaygisiz, Sule Aydin, Cigdem Cengelli, Cigdem Toprak, Kevser Erol Eskisehir Osmangazi University, Faculty of Medicine, Department of Pharmacology, Eskisehir, TURKEY Abstract It was reported that nitric oxide, acting as a neuromodulator and neurotransmitter in central nervous system, has proconvulsant or anticonvulsant activities in different experimental convulsion models. The aim of the present study was to investigate the role of nitric oxide pathway on the anticonvulsant activities of valproic acid, gabapentin and phenytoin and also agmatine suggested as an anticonvulsant agent. Swiss albino mice were used for the study. Seizures were induced by single intraperitoneal injection of 45mg/kg penthylenetetrazole (PTZ). The existence of myoclonic jerk (MJ) and generalized tonic-clonic convulsions (GTCC) were recorded. Single doses of agmatine (10 mg/kg), valproic acid (150 mg/kg), gabapentin (20 mg/kg) and phenytoin (20 mg/kg) alone or with the precursor of nitric oxide, L-arginine (60 mg/kg) or non-specific nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg) were injected intraperitoneally. Agmatine and valproic acid significantly prevented but phenytoin and gabapentin did not prevent the GTCC and MJ. L-arginine reduced the activity of agmatine on MJ but did not have any activity on GTCC. L-NAME did not affect the activity of agmatine on both MJ and GTCC. Both L-Arginine and L-NAME did not affect the activity of valproic acid and phenytoin on both MJ and GTCC. L-Arginine did not change the activity of gabapentin on both MJ and GTCC. L-NAME increased the activity of gabapentine on both MJ and GTCC. This study suggested that nitric oxide may have a role on the anticonvulsant activity of agmatine and gabapentin but not those of valproic acid and phenytoin.It was reported that nitric oxide, acting as a neuromodulator and neurotransmitter in central nervous system, has proconvulsant or anticonvulsant activities in different experimental convulsion models. The aim of the present study was to investigate the role of nitric oxide pathway on the anticonvulsant activities of valproic acid, gabapentin and phenytoin and also agmatine suggested as an anticonvulsant agent. Swiss albino mice were used for the study. Seizures were induced by single intraperitoneal injection of 45mg/kg penthylenetetrazole (PTZ). The existence of myoclonic jerk (MJ) and generalized tonic-clonic convulsions (GTCC) were recorded. Single doses of agmatine (10 mg/kg), valproic acid (150 mg/kg), gabapentin (20 mg/kg) and phenytoin (20 mg/kg) alone or with the precursor of nitric oxide, L-arginine (60 mg/kg) or non-specific nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg) were injected intraperitoneally. Agmatine and valproic acid significantly prevented but phenytoin and gabapentin did not prevent the GTCC and MJ. L-arginine reduced the activity of agmatine on MJ but did not have any activity on GTCC. L-NAME did not affect the activity of agmatine on both MJ and GTCC. Both L-Arginine and L-NAME did not affect the activity of valproic acid and phenytoin on both MJ and GTCC. L-Arginine did not change the activity of gabapentin on both MJ and GTCC. L-NAME increased the activity of gabapentine on both MJ and GTCC. This study suggested that nitric oxide may have a role on the anticonvulsant activity of agmatine and gabapentin but not those of valproic acid and phenytoin. PT603 The contribution of resveratrol to the antiepileptic effects of diazepam and gabapentin Kaygısız B1, Özatik Y2, Özatik O3, Bayraktar D4, Teksoy Ö5, Ç. Çengelli Ünel1, K.Erol1 1Department of Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey 2Department of Pharmacology, Faculty of Medicine, Ahi Evran Üniversity, Kırsehir, Turkey 3Department of Histology and Embryology, Faculty of Medicine, Ahi Evran University, Kırsehir, Turkey 4Department of Physiology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey 5Department of Biology, Faculty of Arts and Sciences, Eskisehir Osmangazi University, Eskisehir, Turkey Abstract Resveratrol (RES), a polyphenolic compound, was reported to have protective effect against convulsions. The effects of resveratrol alone or in combination with low-dose antiepileptics against pentylenetetrazole (PTZ)-induced seizures and its histological effects in brain regions were investigated. Mice were divided into 8 groups: Control, RES (75mg/kg), diazepam (DZ) 0,01, 0,2mg/kg, gabapentin (GBP) 10,20mg/kg, RES+DZ 0,01mg/kg, RES+GBP 10mg/kg. Seizures were induced by 45mg/kg i.p. PTZ administration. RES was given p.o for 7 days. In combination groups, DZ and GBP were applied i.p 30 min after the last dose of RES. Mice were observed for 30 min and seizure severity, seizure existence and mortality rates were evaluated. Cerebellum, cortex, hippocampus were isolated for the histopathological evaluation of necrosis, cell death and hemorrhage. In control group, the rate of seizure existence was determined as 100% whereas in GBP20 and DZ0,2mg/kg groups it wasResveratrol (RES), a polyphenolic compound, was reported to have protective effect against convulsions. The effects of resveratrol alone or in combination with low-dose antiepileptics against pentylenetetrazole (PTZ)-induced seizures and its histological effects in brain regions were investigated. Mice were divided into 8 groups: Control, RES (75mg/kg), diazepam (DZ) 0,01, 0,2mg/kg, gabapentin (GBP) 10,20mg/kg, RES+DZ 0,01mg/kg, RES+GBP 10mg/kg. Seizures were induced by 45mg/kg i.p. PTZ administration. RES was given p.o for 7 days. In combination groups, DZ and GBP were applied i.p 30 min after the last dose of RES. Mice were observed for 30 min and seizure severity, seizure existence and mortality rates were evaluated. Cerebellum, cortex, hippocampus were isolated for the histopathological evaluation of necrosis, cell death and hemorrhage. In control group, the rate of seizure existence was determined as 100% whereas in GBP20 and DZ0,2mg/kg groups it was 22 | International Journal of Neuropsychopharmacology, 2016 14,3% and 0% respectively. The rates were determined as 77,8%, 85,7% and 42,9% in RES, GBP10mg/kg and DZ0,01mg/kg groups respectively and as 71,4% and 57,1% for RES+GBP10mg/kg and RES+DZ0,01mg/kg combination groups respectively. The seizure severity score was 0 in GBP20mg/kg and DZ0,2mg/kg groups. The scores in RES, GBP10mg/kg and DZ0,01mg/kg groups or in combinations of RES with GBP and DZ were determined as 4 and 5. There was no significant difference between groups in terms of the mortality rates. There were acidophylic neurons indicating acute neuronal injury and gliosis in hippocampal CA1, CA3, H, DG regions and cerebellar hemorrhagia in all groups except GBP 20 and DZ 0,2mg/kg groups. GBP 20mg/kg and DZ 0,2mg/kg significantly decreased the seizure severity and provided protection against PTZ-induced seizures. Any preventive effect or any reduction in seizure severity were not observed when RES used alone or in combinations with subeffective doses of GBP and DZ. Histopathological evaluations also supported the behavioral results.