Effects of ethanol drinking on central nervous system functional activity of alcohol-preferring rats Helen J. K. Sable a , Zachary A. Rodd a , Richard L. Bell a , Jonathan A. Schultz a , Larry Lumeng b,c , William J. McBride a,c, * a Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA b Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA c Department of Biochemistry, Indiana University School of Medicine, Indianapolis, IN 46202, USA Received 4 November 2004; received in revised form 17 January 2005; accepted 11 March 2005 Abstract The [ 14 C]-2-deoxyglucose (2-DG) technique was used to assess the rates of local cerebral glucose utilization (LCGU) in key limbic, cerebral cortical, hippocampal, basal ganglionic, and subcortical regions of alcohol-preferring (P) rats following chronic 24-h free-choice ethanol drinking. Adult male P rats were submitted to (1) 8 continuous weeks of two-bottle access to 15% ethanol and water (E-C group); (2) 8 weeks of identical two-bottle access followed by 2 weeks of ethanol deprivation (E-D group); (3) cycles of 2 weeks of two-bottle ethanol access and 2 weeks of deprivation, repeated for four cycles (E-RD group); or (4) water only treatment [ethanol-naive group (E-N group)]. A single pulse of [ 14 C]-2-DG (125 mCi/kg) was administered via a venous catheter, and timed arterial blood samples were collected over 45 min and later assayed for plasma glucose and [ 14 C]-2-DG concentrations. Quantitative autoradiography was used to determine [ 14 C] densities, and LCGU values were calculated. With the exception of a few small differences in the hippocampus, no significant differences were found in any of the central nervous system (CNS) regions examined among the four experimental groups of P rats. Animals in the E-D group had lower LCGU rates in the anterior hippocampal CA1 subregion than animals in the E-N, E-C, and E-RD groups. In the anterior hippocampal CA3 subregion and the anterior hippocampal dentate gyrus, the E-D group had significantly lower LCGU rates than the E-RD group. Overall, the results of this study indicate that 24-h ethanol-drinking experience has little effect on CNS functional neuronal activity in P rats. Ó 2005 Elsevier Inc. All rights reserved. Keywords: Local cerebral glucose utilization; [ 14 C]-2-deoxyglucose; Alcohol-deprivation effect; Quantitative autoradiography; Alcohol-preferring (P) rats 1. Introduction Whole-brain imaging techniques such as positron emission tomography and [ 14 C]-2-deoxyglucose (2-DG) quantitative autoradiography are in vivo procedures used to study functional neuronal activity in human beings and animals, respectively. Both methods are based on the premise that neuronal glucose metabolism is correlated with neuronal activation. Thus, functional central nervous system (CNS) changes are determined by quantifying local cerebral glucose utilization (LCGU) rates in distinct regions of the CNS. Comparisons between rodent lines selectively bred for high and low alcohol preference have revealed a number of neuroanatomical, neurochemical, and electrophysiological differences in key brain regions implicated in ethanol reward (McBride & Li, 1998; Murphy et al., 2002). Using the 2-DG method, significant differences in LCGU rates were not found in ethanol-naive high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) replicate line rats, although there was a tendency for higher LCGU values in many CNS regions of the HAD rats compared to LAD rats (Learn et al., 2001). On the other hand, another study determined that LCGU rates were significantly higher in several limbic, cerebral cortical, and subcortical areas of ethanol-naive alcohol-preferring (P) rats compared to alcohol-nonpreferring (NP) and Wistar rats (Smith et al., 2001a). The results of the present study indicate that selective breeding for divergent ethanol drinking can produce innate differences in functional neuronal activity, but these differences do not generalize to all lines of rats selectively bred for disparate alcohol-drinking behaviors. A single intraperitoneal injection of a low (0.25 g/kg) dose of ethanol produced lower LCGU values in several CNS regions of LAD but not HAD rats from replicate * Corresponding author. Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indian- apolis, IN 46202, USA. Tel.: C1-317-274-3820; fax: C1-317-274-1365. E-mail address: wmcbride@iupui.edu (W.J. McBride). 0741-8329/05/$ – see front matter Ó 2005 Elsevier Inc. All rights reserved. doi: 10.1016/j.alcohol.2005.03.001 Alcohol 35 (2005) 129–135