The most significant differences between male and female rats regarding psychostimulant self-administration behavior are unrelated to biological sex

BackgroundThe goals of this study were to 1) validate the MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model for psychostimulant self-administration (SA), and 2) utilize it to explain the inconsistencies in the observation of sex differences in psychostimulant SA. MethodsWe allowed male and female Long Evans rats (n = 40) to self-administer methamphetamine METH dose 0.1 mg/kg (male n = 9, female n = 18) and saline (male n = 3, female n = 10) via the intravenous route, FR1 schedule, 6 h per day, 5 days per week for 4 weeks. For the MISSING model, we identified behavioral clusters of males and females using normal mixtures clustering analysis of baseline intake, total intake and total intake normalized-to-baseline intake (NBI), followed by unpaired t-tests to compare clusters and Two-way ANOVA to determine if there were any SEX by cluster interactions. For the current model, we grouped our subjects according to biological sex and compared the above variables using unpaired t-tests. For both models, we employed Two-way repeated measures ANOVA and linear regression analysis to analyze SA time course. ResultsFor saline and METH SA, there were no sex differences when we compared males and females generally, with sex differences evident only when we compared sexes from distinct clusters. The current model could not explain the inconsistencies in the observability of sex differences in METH SA. ConclusionsWe validated the MISSING model -it can explain the inconsistencies around sex differences in METH SA.