Age‐ and Sex‐Dependent Effects of Footshock Stress on Subsequent Alcohol Drinking and Acoustic Startle Behavior in Mice Selectively Bred for High‐Alcohol Preference

Abstract

Background Exposure to stress during adolescence is known to be a risk factor for alcohol-use and anxiety disorders. This study examined the effects of footshock stress during adolescence on subsequent alcohol drinking in male and female mice selectively bred for high-alcohol preference (HAP1 lines). Acoustic startle responses and prepulse inhibition (PPI) were also assessed in the absence of, and immediately following, subsequent footshock stress exposures to determine whether a prior history of footshock stress during adolescence would produce enduring effects on anxiety-related behavior and sensorimotor gating. Methods Alcohol-nav̈ve, adolescent (male, n = 27; female, n = 23) and adult (male, n = 30; female, n = 30) HAP1 mice were randomly assigned to a stress or no stress group. The study consisted of 5 phases: (1) 10 consecutive days of exposure to a 30-minute footshock session, (2) 1 startle test, (3) one 30-minute footshock session immediately followed by 1 startle test, (4) 30 days of free-choice alcohol consumption, and (5) one 30-minute footshock session immediately followed by 1 startle test. Results Footshock stress exposure during adolescence, but not adulthood, robustly increased alcohol drinking behavior in both male and female HAP1 mice. Before alcohol drinking, females in both the adolescent and adult stress groups showed greater startle in phases 2 and 3; whereas males in the adolescent stress group showed greater startle only in phase 3. After alcohol drinking, in phase 5, enhanced startle was no longer apparent in any stress group. Males in the adult stress group showed reduced startle in phases 2 and 5. PPI was generally unchanged, except that males in the adolescent stress group showed increased PPI in phase 3 and females in the adolescent stress group showed decreased PPI in phase 5. Conclusions Adolescent HAP1 mice appear to be more vulnerable to the effects of footshock stress than adult mice, as manifested by increased alcohol drinking and anxiety-related behavior in adulthood. These results in mice suggest that stress exposure during adolescence may increase the risk for developing an alcohol-use and/or anxiety disorder in individuals with a genetic predisposition toward high alcohol consumption.

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

“…Studies with cocaine have shown that a range of stress conditions escalate self-administration in rodent models (Boyson et al 2011; Goeders and Guerin 1994; Haney et al 1995; Tidey and Miczek 1996); however, increases in alcohol consumption are generated by more limited stress parameters (Funk et al 2005; Van Erp et al 2001). While other studies have investigated the stress-alcohol link in mice (Chester et al 2008; Croft et al 2005; Sillaber et al 2002), this is the first to delineate conditions of social defeat stress that reliably lead to escalated voluntary ethanol consumption and self-administration in several cohorts of outbred mice.…”

Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats

“…Other modalities of stress (e.g., footshock or restraint) also produce increases in arousal in rodents as measured by the acoustic startle test (Chester et al, 2008; Jiang et al, 2011; Rasmussen et al, 2008). Similar to our results, others have reported stress-induced increases in startle amplitude that last up to ten days post stress exposure (Jiang et al, 2011; Rasmussen et al, 2008).…”

“…Hyperarousal is a hallmark behavioural effect of stress and also of alcohol dependence (Chester et al, 2008; Chester et al, 2005; Davis et al, 2010; Koob, 1999). The acoustic startle response (ASR) is a reflexive reaction to an auditory stimulus that is mediated by the caudal pontine reticular nucleus (Koch, 1999).…”

Animal models of post-traumatic stress disorder and recent neurobiological insights

“…Studies examining physical stressors as animal models of traumatic stress have found mixed results when examining alcohol consumption post-stress. In mice selectively bred for high-alcohol preference (HAP1 lines), footshock stress increases alcohol drinking during adolescence but not adulthood (Chester et al , 2008). Logrip and Zorrilla (2012) have shown that low-drinking animals with a history of stress exposure (light-cued footshock) significantly increased alcohol self-administration following a period of time, suggesting that prior stress exposure sensitizes low drinkers to self-administer alcohol during a subsequent relapse session.…”