Role of nitric oxide in experimental models of psychosis in rats.

The nitric oxide precursor L-arginine reduced amphetamine-induced repetitive behaviors and haloperidol-induced movement stiffness in rats, while enhancing conditioned avoidance. The nitric oxide synthase inhibitor L-NOARG had opposite effects: it increased repetitive behaviors and stiffness but reduced conditioned avoidance. No significant difference was observed between acute and five-day chronic administration of either compound. The authors conclude that nitric oxide has contradictory effects across different psychosis models, and L-arginine may have antipsychotic potential without causing extrapyramidal side effects.

Study at a glance

Abstract

The aim of our study was to investigate the effects of the NO precursor L-arginine and the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NORAG) on amphetamine-induced stereotypy, haloperidol-induced catalepsy and conditioned avoidance response (CAR) in rats. Amphetamine (3 mg/kg i.p.) was used for the induction of stereotypy, while for the induction of catalepsy and CAR, haloperidol (2 mg/kg i.p.) was used. This study was divided into 2 parts--acute administration of L-arginine (150 mg/kg i.p.) and L-NOARG (50 mg/kg i.p.) and chronic administration of L-arginine (150 mg/kg/day i.p.) and L-NOARG (50 mg/kglday i.p.) for 5 days. We found that L-arginine inhibited amphetamine-induced stereotypy and haloperidol-induced catalepsy, but intensified CAR. On the other hand, L-NOARG intensified stereotypy and catalepsy but inhibited CAR. Also, there was no significant difference between the scores of acute and chronic administration of L-arginine and L-NOARG. It is concluded from our study that nitric oxide produces conflicting results on various models of psychosis. L-arginine might be useful as an antipsychotic without causing extrapyramidal symptoms.