Effect of Ursodeoxycholic Acid on Pentylenetetrazole Kindling and Kindling Induced Memory Impairment in Rat

BACKGROUND AND OBJECTIVE: Epilepsy is one of the common diseases of the brain that about 30-40% of patients with epilepsy experience recurent attacks due to drug resistance. Recently, the beneficial effects of Ursodeoxycholic acid on brain disorders have been considered. The aim of this study was to evaluate the effect of Ursodeoxycholic acid(UDCA)on the Pentylenetetrazole (PTZ) induced kindling, and related learning and memory impairments on Morris water maze. METHODS: This experimental study was done on 32 male Winstar rats divided into 4 groups. The first(n=7)and the second(n=9)groups have received three injections of 0.5 ml NaCl or 50 mg/kg of UDCA respectively and third(n=7) and fourth(n=9) groups have received fifteen injections of 0.5 ml NaCl or 50 mg/kg of UDCA respectively. All injections were given intraperitoneally(ip)(every 48 hours). In all groups, chemical kindling were started after third injections. Twenty-four hour after the last injection, spatial memory was investigated in the Morris water maze. FINDING: Fifteen injections of UDCA significantly reduced the seizure stage from 3.5±0.17 to 3.08±0.11 and duration of stages five from 12.37±1.21 to 8.43±1.09 and increased time to reach the stage five seizures from 1021.65±72.07 to 1252.41±49.63 as compared to control group. However, three injections of UDCA have no effect on the kindling process. However, three time administration of UDCA significantly increased reference memory from 18.72±1.2 s to 26.11±1.8 s. CONCLUSION: Ursodeoxycholic acid inhibits chemical kindling and improves kindling induced memory impairment

Investigating the effect of enzymatic elimination of endocannabinoids inhibitors on tonic- colonic seizure provoked by PTZ

BACKGROUND AND OBJECTIVE: In recent years, numerous attempts were done to find new treatment methods for patients with drug-resistant epilepsy. Anandamide (Anandamides; AEA) and di-Arachidonoylglycerol (2-Arachidonoylglycerol; 2-AG) are two major ligands of endocannabinoid system can be produced or deleted by a certain enzymatic pathway. Given the frequency and significance of these endocannabinoid ligands, it seems that endocannabinoid system in the brain can be changed with pharmacologically manipulating in the pathway of these two main ligands. Therefore, the aim of this study was to evaluate the effect of enzymatic elimination of endocannabinoids inhibitors on tonic-clonic seizure caused by PTZ. METHODS: In this exprimental study 35 Adult male wistar rats were used in 4 groups. Tonic-colonic seizure was induced through single intra-peritoneal injection of PTZ (80 mg/Kg). Latency and duration of each five behavioral seizure stages were monitored for 30 minutes. To inhibit Anandamides elimination, URB and LY (URB: 1 mg/kg, LY: 2.5 mg/kg, i.p), to inhibit 2-2-Arachidonoylglycerol&nbsp;degradation WWL and JJKK (JJKK: 1 mg/kg, WWL: 5 mg/kg, i.p), were used, all dissolved in DMSO and injected 15 minutes before PTZ injection. In sham group, PTZ was injected after DMSO.Time and duration of all five behavioral stages of seizure were recorded for 30 minutes. FINDINGS: Delay to stages 4 and 5 in DMSO+PTZ group were 206+39 and 209+39, respectivly. While in JJKK+WWL+DMSO+PTZ group delay to stages 4 and 5 were 630+159 and 726+360, respectivly, which reveald significant increase (p<0.05). In addition, percentage of stage 5 incidence and mortality rate were 91% in DMSO+PTZ group, while both indexes were decreased to 50% in (JJKK+WWL+DMSO) group. CONCLUSION: Contemporary using both WWL and JJKK as inhibitors of 2-Arachidonoylglycerol elimination effectivly reduced tonic- clonic seizure