Impact of adolescent social Isolation on increased risk for alcohol intake and aversion-resistant drinking in males and females

Rationale : Adverse experiences during adolescence, especially social isolation, increases risk for alcohol use disorders (AUDs). Previous rodent studies of adolescent social isolation (ASI) encompassed all stages of adolescence and/or maintained isolation into adulthood, limiting identification of vulnerable stages of adolescence. Utilizing males only, or combining the sexes, also may have contributed to contradictory findings. Objectives : Investigate social isolation restricted to discrete adolescent stages in combination with re-socialization and then persistent alcohol drinking. Determine whether adolescent isolation during specific developmental time periods, with or without subsequent re-socialization, leads to increased alcohol drinking in males or females, examined separately. Methods: Male and female Wistar rats underwent one of six housing conditions: 1) isolation from postnatal day (P)21–42 followed by re-socialization (ASIR-Early), 2) isolation from P42–63 followed by re-socialization (ASIR-Late), or 3) continuous isolation from P21 onward (ASI), or 4-6) one of three appropriate control treatments. Alcohol-related behaviors were assessed in adulthood using intermittent-access two-bottle choice drinking (IAP), limited daily access (LDA-20) procedures, quinine-adulterated aversion-resistant drinking (ARD), and alcohol re-exposure following prolonged abstinence. Results: In general, ASIR-Early and ASI elevated alcohol drinking in males and females, when compared to contemporary controls, during IAP, LDA-20, ARD, and after prolonged withdrawal, while ASIR-Late had largely similar effects as control conditions. However, for females, only ASI led to greater ARD at the highest quinine dose and also increased alcohol drinking after prolonged withdrawal. In contrast, for males, ASIR-Early and ASI had largely similar enhancement of alcohol drinking. Conclusions : Under these conditions, isolation housing that encompassed the early adolescent period produced enduring increases in alcohol-related behaviors, with re-socialization perhaps more protective in females against ARD and elevated intake after abstinence. These results inform future studies that will investigate neural mechanisms underlying ASI-induced enhancement of alcohol drinking.