title: Blockade of nitric oxide synthesis reduces responding for cocaine self-administration during extinction and reinstatement.
abstract: Nitric oxide is a gaseous neurotransmitter that plays a significant role in various forms of synaptic plasticity and may play a role in the behavioral effects of psychostimulant drugs and in cocaine addiction. The course of drug addiction consists of different phases. Relapse into drug-seeking behavior following a period of abstinence is believed to represent one of the major factors leading to the perpetuation of the addictive cycle. In this respect, experimental extinction procedures provide a measure of the motivational properties of drugs as reflected by the persistence of drug-seeking behavior in the absence of the drug and by the reinstatement of responding by non-contingent drug administration. Pretreatment with the nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 50 mg/kg IP twice daily for 4 days) impaired responding for cocaine self-administration when the drug was available and the increase of drug-seeking behavior upon abrupt cessation of cocaine availability observed in control rats was significantly reduced after treatment with L-NAME. In addition, the priming effect of a non-contingent injection of cocaine on extinguished cocaine self-administration was also diminished by the same treatment. The acquisition of cocaine self-administration, in contrast, was not affected by treatment with L-NAME. These observations lend further support to the hypothesis of the involvement of nitric oxide in cocaine addiction and extend previous findings to components of the cocaine addictive cycle associated with relapse.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Orsini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Izzo
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Luigi
authors.initials: L
authors.lastname: Pulvirenti
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005108:Extinction, Psychological / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D003042:Cocaine; D019331:NG-Nitroarginine Methyl Ester