Peer-Rejected Rats Aid Study of Alcohol Relapse in Women

Rejection of adolescent female rats by their peers has long-term effects on alcohol-seeking behavior, according to a study in Alcoholism: Clinical and Experimental Research, and could provide a tool for studying alcohol relapse in humans. There is growing evidence from experimental studies that women who had adverse social experiences in childhood are more susceptible to alcohol relapse following abstinence. This is not observed in men, despite men having higher rates of alcohol dependence overall. Laboratory-bred rodents are important for studying the molecular and neurobiological underpinnings of addiction and alcohol dependence, but few animal studies have assessed the sex-dependent effects of adverse social experiences on later alcohol-seeking behavior. Recently, researchers in Germany have developed a rat model for adolescent peer rejection which has allowed them to study the long-term consequences of these experiences in adult male and female rats.

The research team housed individual adolescent rats of a strain called Wistar with three rats of another, less playful, strain for one month. Although the Wistar rats attempted to initiate social play, their efforts were not reciprocated, mimicking aspects of peer-rejection in humans and resulting in dysregulated social behaviors. During late adolescence, the Wistar rats were rehoused with others of their strain, and their alcohol-seeking and relapse-like behavior was evaluated in adulthood using a standard research protocol. First, the rats underwent alcohol self-administration training, in which they learnt to discriminate between availability of alcohol or water based on the presence or absence of certain stimuli (scents and blinking lights). Next, the alcohol and stimuli were withheld, until the rats stopped attempting to access the alcohol. At this point, the stimuli were presented again, and the researchers assessed whether these cues reinstated the alcohol-seeking behavior. This ‘alcohol reinstatement paradigm’ is a model for relapse-like behavior in humans. All procedures were conducted in accordance with animal welfare guidance.

Peer-rejection induced long-term, sex-dependent effects on alcohol reinstatement, such that peer-rejected female rats showed an increased reinstatement effect, while peer-rejected males showed a decreased effect. Peer-rejected female rats therefore appear vulnerable to alcohol-seeking and relapse-like behaviors, while male rats appear to buffer the peer-rejection effect and demonstrate resilience to later-life alcohol-seeking behaviors. These are similar to clinical findings in humans. Although the rat peer-rejection model cannot fully replicate adverse social experiences in human adolescence, it does recapitulate behavioral deficits that impact alcohol-seeking behavior later in life. The rat peer rejection model can now be used to study the molecular and neurobiological mechanisms that underpin the sex-dependent effects of adverse social experiences on later alcohol-seeking and relapse-like behavior.

Adverse social experiences in adolescent rats results in persisting sex-dependent effects on alcohol-seeking behavior

Surakka, V. Vengeliene, I. Skorodumov, M. Meinhardt, A. C. Hansson, R. Spanagel (pages xxx)

ACER-20-4705.R2