Nitric oxide mediation of morphine-induced place preference in the nucleus accumbens of rat

Abstract

In the present study, the effects of intra-nucleus accumbens injection of l-arginine, a nitric oxide (NO) precursor, and N G-nitro- l-arginine methyl ester ( l-NAME), a nitric oxide synthase (NOS) inhibitor, on morphine-induced conditioned place preference in male Wistar rats were investigated. Our data showed that subcutaneous (s.c.) injection of morphine sulphate (0.5–10 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intra-accumbens administration of l-arginine (0.03 and 0.05 μg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited significant conditioned place preference, while intra-accumbens administration of l-NAME (0.3, 0.1 and 1 μg/rat) decreased the acquisition of conditioned place preference induced by morphine (7.5 mg/kg). The response to different doses of l-arginine was decreased by l-NAME (0.03 μg/rat). l-Arginine and l-NAME by themselves did not elicit any effect on place conditioning. Intra-accumbens administration of l-arginine but not l-NAME significantly decreased the expression of morphine (7.5 mg/kg)-induced place preference. The attenuation of already established morphine-induced place preference on the test day by l-arginine was inhibited by l-NAME. The results indicate that NO may be involved in the acquisition and expression of morphine-induced place preference.