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

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.

Adolescent oxytocin administration reduces depression-like behaviour induced by early life stress in adult male and female rats.

Early life stress (ELS) exposure alters brain development, increasing vulnerability for mental illness in adulthood, including depression. Despite this association, there are no approved pharmacotherapies to protect against the emergence of mental illness resulting from ELS. Recent preclinical work showed that oxytocin (OT) administration in adulthood reduced depressive-like behaviour in male rats with a history of ELS. However, the ability of an OT treatment regime in adolescence, a critical developmental window for the OT system, to prevent the expression of depressive-like behaviours following ELS has not been investigated. Therefore, the present study aimed to determine whether chronic OT administration can ameliorate the enduring effects of ELS on depressive-like behaviours in both male and female rats. Following birth, Long Evans rat pups (N = 107) underwent maternal separation (MS) for either 15 min (MS15) or 6 h (MS360) on postnatal days (PND) 1-21. During adolescence (PND 28-42), rats received a daily injection of either OT (1 mg/kg) or saline. During adulthood (PND 57 onwards), effort-related motivation was measured using a model of effortful choice (EC), while behavioural despair was measured using the forced swim test (FST). Lastly, body and organ weights were measured to examine the physiological impacts of ELS and chronic OT administration. Overall, in both sexes, MS360 increased behavioural despair yet had no impact on effort-related motivation. Importantly, adolescent OT administration prevented the MS360-induced increase in behavioural despair in both males and females. Additionally, MS360 resulted in persistent reductions in body weight in both sexes post-weaning and increased spleen weight in males and adrenal weight in females. OT treatment had no impact on body weight in either sex, but prevented the MS-induced increase in adrenal gland weight in females. Overall, these findings have important implications for using oxytocin as a preventative pharmacotherapy after ELS.