We propose to investigate the involvement of nicotinic acetylcholine receptors (NAChR) in i) the consumption of alcohol, and ii) the subjective responses to alcohol in human social drinkers. Prior research has indicated an unequivocal relationship between nicotine and alcohol consumption with the use of one increasing the likelihood that the other will be consumed as well. Experimental studies in animals have repeatedly shown that alcohol consumption increases when a nicotine pretreatment is administered and recently a corresponding effect has been found in human social drinkers. It has been hypothesized that nicotine may alter the subjective responses to alcohol and that the stimulant-like effects and euphorigenic properties of alcohol may be mediated through action at NAChRs. The proposed studies will examine this relationship between the stimulant-like effects and consumption of alcohol and nicotinic acetylcholine function through two different approaches: nicotine administration and receptor blockade. Mecamylamine, a non-competitive, nicotinic receptor antagonist that readily passes the blood-brain barrier, will be administered in two studies to assess the effect of NAChR blockade on the subjective effects of alcohol and its consumption. We will investigate the efficacy of mecamylamine in attenuating the stimulant-like and euphorigenic properties of alcohol as well as its voluntary consumption. The third study proposed will administer nicotine through transdermal patches and assess its impact on the effects and consumption of alcohol. The proposed studies can be a significant and important first step in elucidating the interaction between two of the most commonly used drugs in this country. In addition to providing informative data on possible mechanisms mediating the reinforcing effects of alcohol, these studies can also serve as a first step to determining the efficacy of nicotinic antagonists as a treatment for alcohol abuse or dependence.

R03AA013729

2002-09-15

2005-08-31