Abstract
Adolescence marks a particularly vulnerable period to developing substance use disorders. Human and rodent studies suggest that hypersensitivity to reward may contribute towards such vulnerability when adolescents are exposed to casual drug use. Methamphetamine is a popular illicit substance used by male and female youths. However, age- and sex-specific research in methamphetamine is scarce. The present study therefore aimed to examine potential sex differences in methamphetamine-conditioned place preference in adolescent and adult mice. Mice (n = 16–24/group) were conditioned to methamphetamine (0.1 mg/kg). We observed that regardless of age, females were more hyperactive compared to males. Individually normalized score against baseline preference indicated that on average, adolescents formed stronger preference compared to adults in both sexes. This suggests that adolescents are more sensitive to the rewarding effects of methamphetamine compared to adults. Surprisingly, individual data showed that some mice formed a conditioned place aversion instead of preference, with females less likely to form an aversion compared to males. These results suggest that adolescents may be hypersensitive to methamphetamine’s rewarding effects. In addition, female resistance to the aversive effects of methamphetamine may relate to the sex-specific findings in humans, including quicker transition to regular methamphetamine use observed in females compared to males.
Highlights
Methamphetamine is the most widely used illicit substance globally other than cannabis (United Nations Office on Drugs and Crime, 2017a)
Methamphetamine Conditioned Place Preference prevalence of methamphetamine use is often similar in males and females across different countries (Compton et al, 2007; Courtney and Ray, 2014; Australian Institute of Health and Welfare, 2017; Papamihali et al, 2021)
We investigated age and sex differences in Conditioned place preference (CPP) and locomotor activity to 0.1 mg/kg methamphetamine in mice
Summary
Methamphetamine is the most widely used illicit substance globally other than cannabis (United Nations Office on Drugs and Crime, 2017a). Youth use is high (Degenhardt et al, 2016; United Nations Office on Drugs and Crime, 2017b; Australian Institute of Health and Welfare, 2020), which is a significant public and social health concern. Methamphetamine Conditioned Place Preference prevalence of methamphetamine use is often similar in males and females across different countries (Compton et al, 2007; Courtney and Ray, 2014; Australian Institute of Health and Welfare, 2017; Papamihali et al, 2021). Females transition more rapidly from initial to problematic methamphetamine use and are more sensitive to its acute subjective and behavioral effects compared to males (Brecht et al, 2004; Mayo et al, 2019)
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