Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice

Abstract

Both rewarding and aversive effects contribute to alcohol consumption. Animals genetically predisposed to be high drinkers show reduced sensitivity to the aversive effects of alcohol, and in some instances, increased sensitivity to alcohol's rewarding effects. The present studies tested the high drinking in the dark (HDID) selected lines, a genetic model of drinking to intoxication, to determine whether intake in these mice was genetically related to sensitivity to alcohol aversion or reward. Male HDID mice from the first and second replicate lines (HDID-1 and HDID-2, respectively) and mice from the heterogeneous progenitor control population (HS/Npt, or HS) were conditioned for a taste aversion to a salt solution using two doses of alcohol, and lithium chloride (LiCl) and saline controls. In separate experiments, male and female HDID-1, HDID-2 and HS mice were conditioned for place preference using alcohol. HDID mice were found to have an attenuated sensitivity to alcohol at a moderate (2 g/kg) dose compared to HS mice, but did not differ on conditioned taste aversion to a high (4 g/kg) dose or LiCl or saline injections. HDID and HS mice showed comparable development of alcohol-induced conditioned place preference. These results indicate that high blood alcohol levels after drinking in the HDID mice is genetically related to attenuated aversion to alcohol, while sensitivity to alcohol reward is not altered in these mice. Thus, HDID mice may find a moderate dose of alcohol to be less aversive than control mice and consequently may drink more because of this reduced aversive sensitivity.

Keywords: alcohol; behavioral genetics; binge drinking; conditioned place preference; conditioned taste aversion; selected lines.

Fig. 1

NaCl solution intake in ml/kg body weight across the 6 conditioning trials. Panel a shows intake for the HDID-1 mice and panel b shows intake for the HS mice. Ethanol conditioning groups (2 and 4 g/kg) are shown in filled symbols and control groups (vehicle and LiCl) are shown in open symbols. Means +/− SEM shown. * indicates a statistically significant difference (p≤0.001) in NaCl solution intake from corresponding HS group.

Fig. 2

NaCl solution intake in ml/kg body weight across the 6 conditioning trials. Panel a shows intake for the HDID-2 mice and panel b shows intake for the HS mice. Ethanol conditioning groups (2 and 4 g/kg) are shown in filled symbols and control groups (vehicle and LiCl) are shown in open symbols. Means +/− SEM shown. * indicates a statistically significant difference (p≤0.01) in NaCl solution intake from corresponding HS group.

Fig. 3

Ethanol conditioned place preference expression during the pretest and Tests 1–3 (after 4, 6, or 8 pairings, respectively). Panels a and b show time spent on the grid floor by male (a) and female (b) animals of each genotype. G+ indicates mice that received 2 g/kg ethanol paired with the grid floor (GRID+ conditioning subgroup) and G- indicates mice that received 2 g/kg ethanol paired with the hole floor (GRID− conditioning subgroup). The difference between G+ and G-group scores reflects the magnitude of conditioned place preference. Panels c and d show percent time spent on the drug-paired floor (collapsed on conditioning subgroup) for males (c) and females (d) of each genotype. The dashed line at 50% indicates the point of no preference for either floor. Means +/− SEM shown.

Fig. 4

Average locomotor activity counts (beam breaks) per minute during the pretest and each place preference test (T1–3) for males (a) and females (b). Means +/− SEM shown.