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


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

Pubmed Central 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