The effect of nitric oxide synthase inhibitor on amphetamine-induced behavioral changes and prodynorphin gene expression in the nucleus accumbens and striatum of the rat has been studied. 2. L-NAME attenuated behavioral stereotypic activity evoked by amphetamine administration. 3. Acute amphetamine administration (5mg/kg i.p.) increased the prodynorphin mRNA level in the nucleus accumbens and striatum after 3 hr. 4. A nitric oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME, 10, 50 mg/kg i.p.) had no effect on the level of prodynorphin mRNA, but prevented dose-dependently the amphetamine-induced increase in prodynorphin gene expression in both the nucleus accumbens and the striatum. 5. These data indicate that inhibition of the nitric oxide pathway attenuates biochemical and behavioral effects of amphetamine.