Nicotine increases alcohol self-administration in non-dependent male smokers
Introduction
The two most commonly abused substances in the general population, alcohol and nicotine, are frequently co-administered (e.g., Batel et al., 1995). The prevalence of tobacco smoking in alcoholics is thought to be as high as 90%, compared to less than 30% in the general population (e.g., Sobell et al., 1990, Romberger and Grant, 2004). Similarly, smokers are 50% more likely to drink regularly than adult non-smokers (Kozlowski and Ferrence, 1990). Some evidence suggests that these associations reflect an ability of ethanol and nicotine administration to increase motivation to obtain the other substance. In smokers, acute alcohol administration is consistently reported to increase cigarette self-administration (Griffiths et al., 1976, Mello et al., 1980, Keenan et al., 1990). In comparison, the converse association is less well understood. There are several reports that, in rodents, chronic or repeated nicotine administration increases alcohol consumption (Smith et al., 1999, Le et al., 2000, Le et al., 2003, Clark et al., 2001, Soderpalm et al., 2000), but this effect has not been uniformly replicated, and decreased alcohol self-administration has also been reported (Sharpe and Samson, 2002). Similarly, acute nicotine administration has been reported to increase (Gauvin et al., 1993), decrease (Nadal et al., 1998), and have no effect on alcohol intake (Nadal and Samson, 1999). Such inconsistent findings may be related to differences in doses, administration regimens, or rodent strains (Le, 2002). The contribution of these factors to the co-administration of nicotine and alcohol in humans remains unknown; to our knowledge, the effect of nicotine on alcohol self-administration in humans has yet to be determined. In a previous investigation acute cigarette smoking was found to increase alcohol related responding in male social drinkers (Perkins et al., 2000). However, because this study did not have a placebo smoking condition it was not possible to determine the extent to which the findings resulted from a pharmacological effect of nicotine.
In the present study, we sought to determine how nicotine delivered by tobacco smoke influences alcohol administration in humans using a double-blind placebo controlled repeated measures procedure, in which cigarettes made of nicotine-containing or denicotinized tobacco were smoked throughout the course of a drinking session. Since nicotine withdrawal may affect alcohol craving and consumption in dependent smokers (Palfai et al., 2000; see also Cooney et al., 2003, Colby et al., 2004), the present protocol examined non-dependent occasional smokers to avoid this potential confound.
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Participants
Fifteen non-dependent male ‘occasional’ smokers (80% Caucasian) between the ages of 18 and 30 (mean = 22.3 ± 1.8) were recruited from the community through advertisements placed in local community newspapers and on university websites. All were medically healthy, free from current or previous mental illness including past or present substance use disorders (including nicotine dependence) as determined by a semi-structured clinical interview using DSM-IV criteria (First et al., 1995), and all scored
Alcohol and water self-administration
Because the behavioural PR data increase geometrically, the data were screened for normality. Using the Kolmogorov–Smirnov method, it was determined that each PR distribution was satisfactorily normal (P > 0.05) and this was confirmed through an inspection of the skewness and kurtosis of each variable (all absolute values < 2). To screen for outliers, Z-scores were calculated on the relative difference scores for PR responding in the two conditions (nicotine–denicotinized) and no outliers were
Discussion
In this study, nicotine administration via tobacco smoke increased alcohol consumption in a significant majority of the participants. While these findings are consistent with data demonstrating increased overall levels of alcohol consumption among smokers (e.g., Batel et al., 1995), to our knowledge this is the first placebo-controlled study to demonstration that nicotine acutely increases alcohol ingestion in humans.
Although the present study did not directly assess the mechanisms underlying
Acknowledgments
This research was supported by an operating grant from the Canadian Institutes of Health Research to R.O.P. and M.L. M.L. is the recipient of a salary award from the Fonds de la Recherche en Santé du Québec.
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