CONSTANT LIGHT EXPOSURE POTENTIATES ETHANOL CONSUMPTION AND PREFERENCE FOR ETHANOL IN THE MOUSE

1. CONSTANT LIGHT EXPOSURE POTENTIATES ETHANOL CONSUMPTION AND PREFERENCE FOR ETHANOL IN THE MOUSE K.L. Miller1, A.J. Brager1, M.A. DePaul1, R.A. Prosser2, and J.D. Glass1. 1Dept Biological Sciences, Kent State University, Kent, OH, 2Dept Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN. INTRODUCTION The expression of per2 is a critical component of circadian clock functioning. Exposure to constant light reduces the circadian expression of per2, while reduced expression of per2 potentiates alcohol consumption. Moreover, increased alcohol consumption markedly disrupts sleep homeostasis and circadian timing, and has broad physiological effects on hormone secretion (e.g. melatonin and cortisol). Given this information, our experimental goals are two fold: 1) to measure ethanol consumption, and 2) to analyze the preference for ethanol during exposure to a 12:12 L:D (LD) photocycle and constant light in the C57BL/6J mouse. METHODS Ethanol Treatment. Male mice (n=11) were given a choice between a 15% ethanol solution dissolved in their drinking water or tap water. Ethanol consumption was measured daily to the nearest 0.25 mL at the beginning of the subjective night. Position of the drinking bottle was controlled. An ethanol preference ratio was calculated: (daily ETOH consumption/daily total fluid consumption). Photocycle. The experiment was divided into two phases; Phase 1:Mice were housed under the LD photocycle for 2 wks. Phase 2: Mice were exposed to constant light (270 lux) for the remaining 2 wks. General circadian locomotor activity was measured using a passive infrared motion detector interfaced with a computerized data acquisition system. RESULTS Constant Light Exposure Potentiates Ethanol Consumption.Mice consumed significantly more ethanol in phase 2 vs. phase 1 (4.79 +/- 0.42 g/kg vs. 3.24 +/- 0.18 g/kg, respectively; p<0.01). Treatment differences were observed on days 3, 4, and 12. Constant Light Exposure Increases Ethanol Preference.Preference for ethanol was greater in phase 2 vs. phase 1 (0.25 +/- 0.01 vs. 0.19 +/- 0.01, respectively; p<0.01). Treatment differences were observed on days 3, 4, and 11. A positioning effect was also observed; preference for ethanol was greater on the left vs. right (0.24 +/- 0.01 vs. 0.21 +/- 0.01, respectively; p<0.04). Figure 2: Representative actogram is shown. Shaded yellow demarcates exposure to constant light. As illustrated, constant light altered the robustness of circadian locomotor activity. Figure 2: Schematic annotates the broad influence the environment and clock genes have on circadian clock functioning and drug addiction and reward. As shown, residual environmental disruptions facilitate the development of sleep and circadian disorders by means of altering clock gene expression. These disruptions, in turn, augment ethanol consumption and increase the risk of alcohol abuse and dependence. • CONCLUSIONS • Constant light exposure: • Potentiates ethanol consumption • Increases preference for ethanol • Alters the robustness of circadian locomotor activity Figure 1: Ethanol consumption (top), water consumption (middle), and ethanol preference (bottom) with respect to photoperiod are shown. Constant light exposure augmented ethanol consumption and preference. Asterisks annotate day of treatment effects (p<0.05). Acknowledgements: NIH grant AA015948 to RAP and JDG