Prairie voles as a novel model of socially facilitated excessive drinking

Abstract

Social relationships strongly affect alcohol drinking in humans. Traditional laboratory rodents do not exhibit social affiliations with specific peers, and cannot adequately model how such relationships impact drinking. The prairie vole is a socially monogamous rodent used to study social bonds. The present study tested the prairie vole as a potential model for the effects of social affiliations on alcohol drinking. Same-sex adult sibling prairie voles were paired for five days, and then either separated into individual cages, or housed in pairs. Starting at the time of separation, the voles received unlimited access to alcohol in a two-bottle choice test versus water. Pair-housed siblings exhibited higher preference for alcohol, but not saccharin, than singly housed voles. There was a significant correlation between the amount of alcohol consumed by each member of a pair when they were housed together (r = 0.79), but not when housed apart (r = 0.20). Following automated analysis of circadian patterns of fluid consumption indicating peak fluid intake before and after the dark phase, a limited access two-hour two-bottle choice procedure was established. Drinking in this procedure resulted in physiologically relevant blood ethanol concentrations and increased Fos immunoreactivity in perioculomotor urocortin containing neurons (but not in nucleus accumbens or central nucleus of the amygdala). The high ethanol preference and sensitivity to social manipulation indicate that prairie voles can serve to model social influences on excessive drinking.

Figure 1. Alcohol elimination rate in prairie voles and C57BL/6J mice

A) Blood ethanol concentration (BEC) following 2.5 g/kg i.p. injection of ethanol, in naïve prairie voles and mice (n = 4-5 per group per time point). B) BEC following 2.5 g/kg i.p. injection of ethanol in prairie voles and mice that had previously self-administered alcohol orally (n = 7-10 per group per time point). Values represent mean ± SEM; lines indicate linear regression, and rate of ethanol elimination; ‘X’ indicates X-intercept. * Slopes are significantly different (p < 0.01). # Intercepts are significantly different (p < 0.05).

Figure 2. Alcohol drinking in same-sex sibling pairs, housed together with a mesh divider, or separated from sibling

A) Alcohol preference for females and males housed with a sibling (checkered bars) or separated from a sibling (solid bars), at increasing concentrations of ethanol (3%, 6%, 10%). B) Alcohol consumption (g/kg) for females and males housed with a sibling (checkered bars) or separated from a sibling (solid bars), at increasing concentrations of ethanol (3%, 6%, 10%). C) Saccharin and quinine preference for females and males housed with a sibling (checkered bars) or separated from a sibling (solid bars). Values represent mean + SEM; number of animals per group per concentration is indicated. * Effect of housing (p < 0.01). # Effect of housing (p < 0.05). + Effect of sex (p < 0.05).

Figure 3. Fluid consumption of prairie vole partners

Correlation of consumption of A) alcohol (10% ethanol), B) saccharin, and C) quinine between siblings in each housing condition. Values represent the average dose of each substance consumed by an individual vole per day, during four days for alcohol and two days for saccharin and quinine.

Figure 4. Fluid intake and the circadian cycle

A) Average intake of saccharin, water, and total fluid, collapsed across days 3-4 of testing with saccharin. B) Average intake of ethanol, water, and total fluid, collapsed across days 1-4 of testing with ethanol. Values represent number of licks per hour for all animals, indicating mean ± SEM; n = 24. X-axis values represent number of hours from ‘lights off’ time. Horizontal black bars indicate the dark phase of the circadian cycle. Vertical dotted lines indicate the time at which fluids were replaced between successive test days.

Figure 5. Solution preference ratios by fluid consumption and recorded licks

Correlation of preference ratios for A) saccharin and B) 10% ethanol over water, calculated from fluid consumption by number of licks recorded (X-axis) and by weight (Y-axis) for each solution. Values represent individual animal preference for each day.

Figure 6. Fos immunoreactivity after limited access to alcohol

Induction of Fos by alcohol self-administration was inspected by comparing immunohistochemical staining in brains of alcohol-naïve voles (A,C,E) to that of voles after two-hour access to alcohol (B,D,F) at 20X magnification. Very little induction was observed in the nucleus accumbens (A,B) or central nucleus of the amygdala (C,D), but there was apparent induction of Fos in the perioculomotor urocortin containing neurons (E,F). Arrows indicate examples of Fos positive nuclei.

Figure 7. Fos IR as a measure of alcohol consumption

Fos immunoreactivity in limited-access alcohol drinking voles compared to naïve animals, in A) nucleus accumbens B) central nucleus of the amygdala and C) perioculomotor urocortin containing neurons. Values represent mean number of Fos-positive cells + SEM; number of animals per group is indicated. * Difference between groups (p < 0.01).