Neuronal nitric oxide synthase inhibition decreases cocaine self-administration behavior in rats
Neuronal nitric oxide synthase inhibition decreases cocaine self-administration behavior in rats
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DOI：
10.1007/s00213-001-0935-8
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Kantak, KM
中科院分区：
文献类型：
--
作者：
Collins, SL;Kantak, KM
Rationale: 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. Objectives: 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). Methods: Rats were trained to self-administer I 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. Results: 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. Conclusions: By selectively reducing drug-seeking behavior, these data sue-est that 7-NI may enhance the reinforcing effects of cocaine.
