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. 2009 Sep;34(10):2218-26.
doi: 10.1038/npp.2009.49. Epub 2009 May 13.

Dopamine and serotonin transporter availability during acute alcohol withdrawal: effects of comorbid tobacco smoking

Kelly P Cosgrove  1 , Erica Krantzler, Erin B Frohlich, Stephanie Stiklus, Brian Pittman, Gilles D Tamagnan, Ronald M Baldwin, Frederic Bois, John P Seibyl, John H Krystal, Stephanie S O'Malley, Julie K Staley
Affiliations

Dopamine and serotonin transporter availability during acute alcohol withdrawal: effects of comorbid tobacco smoking

Kelly P Cosgrove et al. Neuropsychopharmacology. 2009 Sep.

Abstract

Tobacco smoking is highly comorbid with heavy alcohol drinking, yet the interaction of tobacco smoking and alcohol drinking on brain catecholaminergic synaptic markers is unexplored. Here we evaluate the effects of alcohol drinking alone from comorbid alcohol drinking and tobacco smoking on dopamine (DA) and serotonin (5-HT) transporter availability. A total of 14 heavy alcohol drinking smokers (n=6) and nonsmokers (n=8) and 14 age-matched control smokers (n=6) and nonsmokers (n=8) were imaged with [(123)]beta-CIT single photon emission computed tomography. Alcohol drinking smokers and nonsmokers consumed 134.3+/-100.3 and 196.5+/-139.9 drinks, respectively, over the previous month and were imaged during acute withdrawal, eg within 5 days of their last drink. Striatal DA transporter availability was significantly higher (16%, P=0.04) in alcohol drinkers compared to controls. 5-HT transporter availability was also significantly higher in alcohol drinkers vs controls in the brainstem (25%, P=0.001) and the diencephalon (8%, P=0.01). This elevation was restricted to alcohol drinking nonsmokers with higher DA transporter availability in the striatum (26%, P=0.006), and higher 5-HT transporter availability in the diencephalon (26%, P=0.04) and brainstem (42%, P<0.0002). There was a significant positive correlation between days since last drink and 5-HT transporter availability in the diencephalon (r=0.60, P=0.023) and brainstem (r=0.54, P=0.047), in the total group of alcohol drinkers and in the nonsmokers, but not the smokers. During the first week of abstinence, DA and 5-HT transporter availability is higher in alcohol drinking nonsmokers but not in alcohol drinking smokers. Smoking appears to suppress neuroadaptive changes in DA and 5-HT transporters during acute withdrawal from alcohol.

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Conflict of interest statement

Disclosures/ Conflict of Interest: Dr. Krystal serves as a consultant to Astra-Zeneca, Bristol-Myers Squibb, Cypress Bioscience, Inc., Eli Lilly and Co., Forest Laboratories, Glaxo-SmithKline, Houston Pharma, Janssen Research Foundation, Lohocla Research Corporation, Merz Pharmaceuticals, Organon Pharmaceuticals/Division of Schering-Plough Research Institute, Pfizer Pharmaceuticals, Schering Corporation acting through Schering-Plough Research Institute Division, Shire Pharmaceuticals, Takeda Industries, Tetragenex Pharmaceuticals, Transcept Pharmaceuticals, UCB Pharma, and US Micron. Dr. Krystal has patents pending for glutamatergic agents for psychiatric disorders and oral ketamine for depression. No other authors report any conflicts of interest.

Figures

Figure 1
Figure 1
Striatal [123I]β-CIT binding in controls and alcohol drinkers in the total group and by smoking status. a. The bar represents the mean in each group. Percent difference was calculated as [(alcohol drinker – control)/alcohol drinker x 100]. In the total group, there was a 16% difference (P=0.04), in the nonsmokers a 26% difference (P=0.006), and in the smokers a 1% difference (P=1.0).
Figure 2
Figure 2
Diencephalon and brainstem [123I]β-CIT binding in controls and alcohol drinkers in the total group and by smoking status. a. In the total group, there was an 8% difference (P=0.01), in the nonsmokers a 26% difference (P=0.04), and in the smokers a −28% difference (P=0.30). b. In the total group, there was a 25% difference (P=0.001), in the nonsmokers a 42% difference (P<0.0002), and in the smokers a −13% difference (P=0.90).
Figure 3
Figure 3
Diencephalon and brainstem [123I]β-CIT binding in alcohol drinkers in the total group and by smoking status as a function of days since last drink. a. Significant linear regression coefficients were found in the total group and in the nonsmokers, but not the smokers for both brain regions.
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