Neuronal nitric oxide synthase inhibition decreases cocaine self-administration behavior in rats

• Published in: Psychopharmacologia Vol. 159; no. 4; pp. 361 - 369
• Main Authors: Collins, Stephanie, Kantak, Kathleen
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.2002; Springer Nature B.V
• Subjects: Animals; Behavior, Addictive - drug therapy; Behavior, Addictive - enzymology; Behavior, Addictive - psychology; Biological and medical sciences; Cocaine; Cocaine - administration & dosage; Dopamine; Dopamine D1 receptors; Dopamine Uptake Inhibitors - administration & dosage; Dose-Response Relationship, Drug; Drug abuse; Drug addiction; Drug addictions; Drug delivery; Drug dosages; Drug self-administration; Enzyme Inhibitors - therapeutic use; Food selection; Indazoles - therapeutic use; Male; Medical sciences; Nitric oxide; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type I; Nitric-oxide synthase; Rats; Rats, Wistar; Second-order schedule; Self Administration - psychology; Toxicology; Agonist; Intraperitoneal administration; Intravenous administration; Rat; Psychotropic; Toxicity; Self administration; Searching behavior; Learning; Ester; Acquisition process; Reinforcement; Drug of abuse; Antagonist; Mechanism of action; Consumption; Drug addiction; CNS stimulant; Enzyme; Illicit drug; Rodentia; D1 Dopamine receptor; Enzyme inhibitor; Instrumental conditioning; Indazole derivatives; Nitric-oxide synthase; Vertebrata; Mammalia; Animal; Cocaine; Oxidoreductases
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-001-0935-8

Inhibitors of nitric oxide synthase (NOS) have been shown to alter behaviors related to cocaine addiction, including its self-administration. However, previous studies have largely used mixed-action NOS inhibitors and have not examined the effects of a neuronal NOS inhibitor on cocaine self-administration. Pretreatment with the neuronal NOS inhibitor 7-nitroindazole (7-NI) was used and its effects on cocaine self-administration were compared with those produced by pretreatment with an indirect dopamine receptor agonist (cocaine) and a D(1)-like dopamine receptor antagonist (SCH 23390). Rats were trained to self-administer 1 mg/kg cocaine under a second-order schedule of drug delivery, which measures drug-seeking behavior independently from drug intake. Pretreatment with various doses of 7-NI, cocaine, and SCH 23390 were tested in combination with the training dose of cocaine followed by studies examining the effects of a selected dose of each pretreatment drug in combination with a range of cocaine doses. Other rats were trained under a second-order schedule of food pellet delivery and pretreated with 7-NI, cocaine, or SCH 23390 to determine the behavioral specificity of the effects of these drugs for cocaine-maintained responding. The results demonstrated that 7-NI reduced responses maintained by the cocaine training dose and produced a downward shift in the cocaine dose-response curve. Changes in drug intake were minor by comparison. Cocaine pretreatment produced effects similar to 7-NI, while the changes observed after SCH 23390 pretreatment were different from 7-NI and cocaine. The reductions in cocaine-maintained responding after 7-NI pretreatment were behaviorally specific because there was no effect of 7-NI on food-maintained responding within the dose range examined. By selectively reducing drug-seeking behavior, these data suggest that 7-NI may enhance the reinforcing effects of cocaine.