Laterality of cortical response to ethanol is moderated by TaqIA A1 allele

Abstract

Acute ethanol releases dopamine, implicated in drug-related reinforcement, and suppresses glucose metabolism, particularly within the right cerebral hemisphere (Volkow et al., 2008; Volkow et al., 2006). This is consistent with a predominance of left hemisphere activity being associating with positive affect or approach, and right hemisphere predominance with negative affect/avoidance (Davidson, 2002; Tomer et al., 2008). Despite substantial evidence linking the Taq1 DRD2 A1 allele with lower dopaminergic tone and greater vulnerability to alcoholism (Noble, 2000), its role in modulating acute effects of alcohol is unknown. We hypothesized that in individuals with the A1 allele, acute ethanol would improve mood and alter relative hemispheric activity. Twelve healthy right-handed white men (mean age [sd]= 29.0 [5.0]) with no history of psychiatric diagnosis or dependence on alcohol had TaqI A DRD2 alleles assessed from blood. Six had the A1A2 genotype (A1+) and six the A2A2 genotype (A1-). In two order-counterbalanced [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET- Siemens ECAT EXACT HR+ tomography; CTI, Knoxville, TN) sessions 10 ± 8 days apart, globally-scaled counts served as a surrogate marker of relative glucose metabolism while participants performed a 35-min auditory vigilance task. Five min before testing, participants drank 250-ml of diet soda containing either 0.75 g/kg body weight or a trivial dose of ethanol, and self-rated their anxiety and fatigue (McNair et al., 1971). Five min after task initiation, FDG (≤5 mCi, ≤185 MBq) was injected intravenously. PET images were acquired for 30 min, and analyzed via statistical parametric mapping software (SPM5; http://www.fil.ion.ucl.ac.uk/spm/software/spm5/), as previously detailed (London et al., 2004). Individual hemispheric comparisons of relative activity within lateral cortex also analyzed 56 anatomical regions-of-interest (ROIs) from a parcellation of MNI-space (Tzourio-Mazoyer et al., 2002). We hypothesized that presence of the A1 allele would influence effects of ethanol on laterality ([Right/(Left+Right)]×100ethanol - [Right/(Left+Right)]×100placebo). Within-subject hemispheric differences were assessed with t-tests. Wilcoxon Signed-Rank tests assessed group differences. Correlation analysis quantified the relationship between ethanol-related change in mood and laterality.