The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.
Nicotinic acetylcholine systems play important roles in addiction, and nicotinic receptor stimulation stimulates dopamine release while the nicotinic antagonist mecamylamine reduces it. Reid et al. [Neuropsychopharmacology 20 (1999) 297.] recently found in human cocaine addicts that mecamylamine reduced cue-elicited cocaine craving. The current study assessed the impact of mecamylamine on cocaine self-administration in rats. Female Sprague-Dawley rats (N=7) were implanted with intravenous (iv) catheters and trained to lever press for cocaine (0.32 mg/kg/infusion FR-1 with a 60-s timeout) in 45-min sessions. After 2 weeks of training, the rats were injected with saline or mecamylamine (1, 2, or 4 mg/kg sc) 10 min before the session. They received the same dose for 1 week with 1 week of uninjected testing between doses. Mecamylamine, compared to saline, significantly (P<.05) reduced the number of cocaine infusions per session with each of these doses. This effect did not appear to be due to a generalized reduction in behavioral activity. Another set of female Sprague-Dawley rats (N=8) were trained to lever press for food reinforcement. In these rats, the 1 and 2-mg/kg mecamylamine doses had no effect on food self-administration. Significant reductions in food self-administration were not seen unless the high dose of 4-mg/kg mecamylamine was used. Nicotinic antagonist treatment reduces cocaine self-administration in rats at doses that do not cause generalized effects on food-reinforced responding. Nicotinic antagonistic treatment may be a useful new approach to treat cocaine addiction.
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
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D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005260:Female; D005502:Food; D008464:Mecamylamine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D003042:Cocaine