Sex differences in sensitivity to the social consequences of acute ethanol and social drinking during adolescence

Abstract

In human adolescents, sociable males frequently drink to enhance positive emotional states, whereas anxious females often drink to avoid negative affective states. This study used a rat model of adolescence to provide information regarding possible sex differences in contributors to social drinking. The effects of ethanol (0, 0.5, and 0.75 g/kg) on play fighting and social preference were assessed on P30, P32, and P34 using a within-subject design. Then animals were tested in a social drinking paradigm (P37-P40), with this testing revealing high drinkers and low drinkers. Sex differences in sensitivity to ethanol emerged among high and low drinkers. High socially drinking males, but not females, when tested prior to drinking sessions, showed significant increases in play fighting at both doses. In low drinking males, play fighting was increased by 0.5 g/kg ethanol, whereas the higher dose of 0.75 g/kg produced significant decreases in play fighting. High drinking females initially showed low levels of social preference than high drinking males and low drinking females and were extremely sensitive to ethanol-induced enhancement of this social measure. Low social drinkers, both males and females, were more sensitive to the suppressing effects of ethanol on social preference following 0.75 g/kg ethanol. These findings indicate that during adolescence enhanced sensitivity to the facilitating effects of ethanol on play fighting is associated with heavy drinking among males, whereas low social preference together with high sensitivity to ethanol-induced enhancement of social preference is related to high social drinking in females.

Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood

“…Using a rat model of adolescence, we have shown that, similar to human findings (e.g., Zehe et al, 2013) initially high socially anxious adolescent females, but not high socially anxious adolescent males, demonstrate enhanced sensitivity to the socially anxiolytic effects of ethanol and high levels of ethanol intake under social circumstances (Varlinskaya et al, 2015a,b). In contrast, repeated exposure to ethanol through early/mid adolescence has long-lasting detrimental consequences in males, but not females (Varlinskaya et al, 2014).…”

“…Ethanol (Experiment 1) or “supersac” (Experiment 2) intake was assessed using a novel social drinking paradigm (Varlinskaya et al, 2015a,b) whereby animals in each cage-mate group were placed together in a novel cage for a 30-min drinking session. During this session, the animals were given free access to two bottles, both containing either 10% ethanol in “supersac” solution (3% sucrose + 0.125% saccharin, see Ji et al, 2008) or “supersac” alone (note: two bottles of the same solution were provided to reduce competition for fluid access within the group during the session).…”

The neurobiology of social play and its rewarding value in rats

“…Moreover, when one accepts that social play facilitates social, emotional and cognitive development, and that male and female animals require distinct (but likely overlapping) social, emotional and cognitive skills in adulthood, then it follows that the neural mechanisms of social play should diverge between male and female animals. Yet, apart perhaps from amygdala function in social play (Kurian et al, 2008; Meaney et al, 1981), effects of alcohol (Varlinskaya et al, 2015) and the role of vasopressin and oxytocin (Bredewold et al, 2014; Veenema et al, 2013), neural underpinnings of sex differences (whereby commonalities between males and females are equally important) have not been studied in detail. One last important question, that partially relates to the previous one, is whether the neural mechanisms of social play behaviour are distinct between species.…”

Sex differences in behavior and neural development and their role in adolescent vulnerability to substance use

“…Interestingly, the effect of ethanol on social interaction predicts voluntary drinking in a sex-specific fashion. A recent study from this same research group found that adolescent males were likely to drink more if they responded to intoxication by increasing play behavior while adolescent females tended to drink more if they were socially anxious at baseline and preferred social contact while intoxicated [64]. These studies suggest that the social environment associated with drinking may influence male and female adolescents differently, with males being especially sensitive to the effects of social play on the reinforcing and aversive properties of ethanol.…”