The effect of adolescent social isolation on vulnerability for methamphetamine addiction behaviours in female rats

Abstract

Rationale Stress exposure during adolescence contributes to developing a methamphetamine (METH) use disorder. However, most of the studies investigating addiction-related behaviours include only male rodents, despite METH addiction rates being higher in females. Furthermore, animal studies investigating the effects of stress on methamphetamine addiction have used only basic self-administration models which may not be sensitive to the effects of stress. Objectives This project explored whether adolescent isolation stress exposure increases the incidence of four key addiction-related behaviours in female rats. Methods Thirty-two female rat pups were caged in groups of four or individually during adolescence from postnatal (PND) day 22, with the latter being re-socialised in groups of four on PND 43. In adulthood, rats were tested for addiction-like behaviours in a METH self-administration paradigm modelling motivation to take METH, persistence in drug-seeking behaviour when METH was not available, resistance to extinction, and propensity to reinstate after a period of withdrawal. Results Adolescent social isolation resulted in lower METH intake during acquisition; however, the paradigm modelling drug-seeking when the drug was unavailable engendered intermittent METH bingeing in all rats, abolishing the group differences in intake during this phase. Adolescent social isolation also accelerated extinction of non-reinforced lever pressing, and increased stress-primed reinstatement, compared to the group-housed rats. Conclusions Adolescent social isolation stress alters various methamphetamine addiction-like behaviours in female rats.

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