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

• Published in: Neuroreport Vol. 9; no. 11; pp. 2485 - 2488
• Main Authors: Itzhak, Yossef, Martin, Julio L, Black, M Dean, Huang, Paul L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott-Raven Publishers 03-08-1998; Lippincott Williams and Wilkins
• Subjects: Animals; Biological and medical sciences; Cocaine - pharmacology; Conditioning, Operant - drug effects; Dopamine Uptake Inhibitors - pharmacology; Enzyme Inhibitors - pharmacology; Indazoles - pharmacology; Male; Medical sciences; Mice; Mice, Knockout; Neuropharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - physiology; Nitric Oxide Synthase Type I; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reinforcement Schedule; Conditioned place preference; CNS stimulant; Enzyme; Psychotropic; Rodentia; Nitric-oxide synthase; Vertebrata; Mammalia; Mouse; Animal; Nitric oxide; Cocaine; Oxidoreductases
• ISSN: 0959-4965; 1473-558X
• DOI: 10.1097/00001756-199808030-00011

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.