The effect of chronic antipsychotic drug administration on nitric oxide synthase activity and gene expression in rat...

Antipsychotic drug treatment may be associated with common and problematic sexual dysfunction, especially impotence, which can diminish quality of life and lead to treatment noncompliance. Nitric oxide synthase (NOS) is an important cellular modulator of erectile function. We have therefore investigated the effect of antipsychotic drug on activity and gene expression of NOS in rat penile tissues. The activity of constitutive NOS was significantly suppressed below control by a 21 days administration of 1 mg/kg haloperidol, which also significantly decreased expression of endothelial NOS (eNOS) and neural NOS mRNA. Risperidone at 0.5 mg/kg also reduced eNOS mRNA expression. Haloperidol or risperidone did not change gene expression and activity of inducible NOS (iNOS). Quetiapine significantly increased activity and mRNA expression of iNOS with 20 and 40 mg/kg doses. These preliminary results have important implications for enhancing our understanding of mechanisms by which antipsychotic drugs induce sexual dysfunction.