Involvement of nicotinic receptors in alcohol self-administration

Background: Alcohol and nicotine, in the form of tobacco. are commonly co-a bused. Nicotinic receptors also have been implicated in alcohol action. We designed the present study to examine the possible involvement of nicotinic receptors in alcohol self-administration. Methods and Results: Pretreatment with lower doses (0.1-0.4 mg/kg) of nicot ine, administered acutely or chronically, did not affect alcohol consumptio n, whereas a higher dose (0.8 mg/kg) initially suppressed alcohol consumpti on but stimulated alcohol consumption on repeated treatment. We observed th e same pattern of nicotine effects on alcohol self-administration using an operant procedure. A dose of 0.8 mg/kg of nicotine initially suppressed ope rant responding for alcohol. Such suppression of alcohol self-administratio n was more pronounced during the first 20 min of the 60 min operant session . Responding for alcohol in the nicotine treated group, however, was signif icantly increased above the saline treated group by the 5th day of treatmen t. Mecamylamine, a noncompetitive nicotinic receptor antagonist, reduced al cohol consumption, whereas dihydro-beta-erythroidine (DH beta E), a competi tive nicotinic receptor antagonist, did nor modify alcohol consumption. Conclusions: The stimulation of alcohol intake induced by nicotine treatmen t and the suppression of alcohol intake induced by mecamylamine provide evi dence for the involvement of nicotinic receptors in alcohol consumption and /or self-administration. The failure of DH beta E to reduce alcohol consump tion, however, suggests that ethanol-nicotine interaction is mediated by ot her nicotinic receptor subtypes rather than alpha 4 beta 2 receptor subtype , or that mecamylamine acts through a nonnicotinic mechanism.