The modulatory effect of nitric oxide in pro- and anti-convulsive effects of vasopressin in PTZ-induced seizures threshold in mice.

Vasopressin neuropeptides play an important role in the several cognitive, social, and neuroendocrine functions. Also, several studies report the involvement of nitrergic system in the vasopressin functions in central nervous system. This study investigates the effect of Arginine-Vasopressin (AVP) in pentylenetetrazol (PTZ)-induced seizures threshold and the probable role of nitric oxide (NO). AVP is administered intraperitoneally (0.01-20μg/kg, i.p.) 30min before induction of seizures. Administration of AVP (0.1μg/kg) significantly lowered the PTZ-induced seizures threshold. But, administration of AVP (10 and 20μg/kg) increased the seizures threshold, significantly. Pretreatment of SR 49059 (V1a receptor antagonist, 2mg/kg, i.p.) just reversed the pro-convulsant effect of AVP. Meanwhile, SSR 149415 (V1b receptor antagonist, 10mg/kg, i.p.) pretreatment reversed both pro-and anti-convulsant effects of AVP. The nitric oxide precursor, L-arginine (60mg/kg, i.p.) increased pro-convulsant effect of AVP, but did not change anticonvulsant activity. The nitric oxide synthase (NOS) inhibitor L-NAME (10mg/kg, i.p.) reversed both pro- and anti-convulsant effect of AVP. Selective inducible NOS inhibitor, aminoguanidine (100mg/kg, i.p.) just reversed the anti-convulsant effects of AVP. The results of the present study showed nitric oxide system may contribute to the biphasic effects of AVP on PTZ-induced seizures. V1a receptor may modulate only the proconvulsive effect. While, V1b receptors can mediate both the pro- and anti-convulsive effect of AVP.