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

• Published in: Psychopharmacology Vol. 239; no. 4; pp. 1129 - 1141
• Main Authors: Webb, Paige I., Hill, Timothy J., Everett, Nicholas A., Thornton, Jade L., Cornish, Jennifer L., Baracz, Sarah J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2022; Springer; Springer Nature B.V
• Subjects: Addictions; Adolescence; Adolescents; Amphetamine-Related Disorders - drug therapy; Analysis; Animals; Biomedical and Life Sciences; Biomedicine; Central Nervous System Stimulants; Child development; Drug abuse; Drug addiction; Drug-Seeking Behavior; Extinction, Psychological; Female; Females; Male; Methamphetamine; Methamphetamine - pharmacology; Motivation; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Psychiatry; Psychological aspects; Rats; Rats, Sprague-Dawley; Reinstatement; Resistance to extinction; Rodents; Self Administration; Social interactions; Social Isolation; Teenagers; Withdrawal; Australia; Adolescence; Addiction; Females; Social isolation; Stress; Methamphetamine
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-022-06103-x

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.