The effect of l-arginine and l-NAME on pentylenetetrazole induced seizures in ovariectomized rats, an in vivo study

The role of ovarian hormones and nitric oxide (NO) on seizure and their interaction have been widely investigated. The present study carried out to evaluate the effect of chronic administration of L-arginine (LA) and L-NAME (LN) on pentylenetetrazole (PTZ) induced epilepsy in ovariectomized (OVX) and naïve female rats. Fourty-eight female rats were randomly divided into six groups (n=8) as follows: (1) sham, (2) ovarectomized (OVX), (3) sham-LA, (4) sham-LN, (5) OVX-LA, and (6) OVX-LN. The animals of sham-LA and OVX-LA received daily injection of 500 mg/kg L-arginine (i.p.) during 4 weeks. Sham-LN and OVX-LN were treated by 10 mg/kg L-NAME (i.p.) daily for 4 weeks. The animals of sham and OVX groups received 1 ml/kg saline (i.p.) instead of L-arginine and L-NAME. The latencies to minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) after intraperitoneal injection of penetylenetetrazole (PTZ, 90 mg/kg) was recorded and compared between groups. A significant increase in the GTCS, but not MCS, latency was seen in OVX rats in comparison with sham-operated animals. Pretreatment of animals with L-NAME resulted in a significant increase in the GTCS and MCS latencies in sham group while no significant effects were seen in OVX rats. On the contrary, while pretreatment with L-arginine had no effects on MCS and GTCS latencies in sham group, a significant decrease in GTCS latency was observed in OVX rats. It is concluded that ovarian sex hormones affect seizure thresholds induced by PTZ and NO has a role on seizures susceptibility following PTZ administration. This NO effect might be differing in the presence or absence of ovarian hormones, but further investigations need to be done.