Increased intake of ethanol and dietary fat in galanin overexpressing mice

Abstract

Evidence suggests that the orexigenic peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN) has a role in stimulating the consumption of ethanol, in addition to a high-fat diet. This possibility was further examined in mutant mice that overexpress the GAL gene. Two sets of GAL-overexpressors (GALOE) compared with wild-type (WT) controls, maintained on laboratory chow and water, were trained to voluntarily drink increasing concentrations of ethanol, from 3 to 15%. In the GALOE versus WT mice, the results revealed the following: (1) a 35-40% increase in ethanol intake and ethanol preference, which was evident only at the highest (15%) ethanol concentration, in male but not female mice, and was seen with comparisons to littermate and nonlittermate WT controls, (2) a significantly larger, 60-75% increase in ethanol intake and ethanol preference after a day of food deprivation, again only in male GALOE mice, (3) no change in consumption of sucrose or quinine solutions in preference tests, and (4) a 55% increase in consumption of a fat-rich diet during a 2-h test period, in both male and female GALOE mice. These results obtained with overexpression of the GAL gene provide strong support for a physiological role of this peptide in stimulating the consumption of ethanol and a fat-rich diet. They reveal gender differences in the behavioral phenotype, which may reflect GAL's functional relationship to reproductive hormones in the stimulation of consummatory behavior.

Keywords: Ethanol intake; dietary fat; galanin; paraventricular nucleus.

Figure 1

Ethanol intake and preference in male and female galanin overexpressing (GALOE) and wild-type (WT) mice voluntarily drinking increasing concentrations of ethanol (3%–15%): (A) Ethanol intake (g/kg/day) in male mice, plotted as a function of ethanol concentration (4-day average) in a two-bottle, continuous-access paradigm; (B) Ethanol intake (g/kg/day) in female mice; (C) Ethanol preference (%) in male mice, calculated as volume of ethanol consumed divided by total volume of solution consumed (x 100); and (D) Ethanol preference (%) in female mice. The male GALOE mice compared to WT, but not female mice, showed a significant increase in ethanol intake and preference on 15% ethanol (*, p<0.01).

Figure 2

Ethanol intake and preference in male and female GALOE compared to WT mice drinking 15% ethanol and tested on the day before food deprivation (pre-depr) and the day after deprivation (post-depr). Compared to WT, the male GALOE mice, but not females, exhibited a significant genotype effect (*, p<0.01) before deprivation, an increase in ethanol intake (+43%, p<0.01, d=3.19) and preference (+45, p<0.01, d=1.99), which became significantly greater after deprivation for intake (+75%, p<0.01, d=5.28) and preference (+65%, p<0.01, d=4.40).

Figure 3

High-fat diet intake (kcal/2h) in male and female GALOE and WT mice during a 2-h test period at dark onset (average of 4 tests), with chow and ethanol removed. Compared to WT, the GALOE males and females exhibited a significant increase in high-fat diet intake (*, p<0.01), and this genotype effect was significantly stronger in females (+56%, p<0.001, d=2.18) compared to males (+29%, p < 0.01, d=1.3).