The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Levin, ED; Mead, T; Rezvani, AH; Rose, JE; Gallivan, C; Gross, R

Published Date

  • December 2000

Published In

Volume / Issue

  • 71 / 5

Start / End Page

  • 565 - 570

PubMed ID

  • 11239676

International Standard Serial Number (ISSN)

  • 0031-9384

Digital Object Identifier (DOI)

  • 10.1016/s0031-9384(00)00382-6


  • eng

Conference Location

  • United States