The role of neuronal nitric oxide synthase in cocaine-induced conditioned place preference.

Previous studies suggested the involvement of the neuronal nitric oxide synthase (nNOS) in the development of sensitization to psychostimulants. In the present study we investigated the role of nNOS in the rewarding properties of cocaine. Swiss Webster mice treated with cocaine (20 mg/kg) and saline every other day for 8 days (four drug and four saline sessions) developed conditioned place preference (CPP) for the drug-paired compartment of the cage. Pretreatment with the nNOS inhibitor, 7-nitroindazole (7-NI; 25 mg/kg), completely blocked cocaine-induced CPP. Mice deficient for the nNOS gene (homozygote nNOS(-/-) mice) were resistant to cocaine-induced CPP, while wild-type nNOS(+/+) mice developed a marked CPP following cocaine administration. Both, the pharmacological and genetic manipulations of nNOS suggest that nitric oxide (NO) is involved in the rewarding properties of cocaine.