Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

Rodent studies have proposed that adolescent susceptibility to substance use is at least partly due adolescents experiencing reduced aversive effects of drugs compared adults. We thus investigated methamphetamine (meth) conditioned place preference/aversion (CPP/CPA) in and adult mice both sexes using a high dose meth (3 mg/kg) or saline as controls. Mice tagged with green-fluorescent protein (GFP) Drd1a Drd2 were used so dopamine receptor 1 (D1) 2 (D2) expression within the insular cortex (insula) could be quantified. There are sex differences how density D1+ D2+ cells insula changes across adolescence may related drug-seeking behaviors. Immunohistochemistry followed by stereology quantify c-Fos and/or GFP insula. Unexpectedly, showed huge variability behaviors including CPA, CPP, no preference aversion. Females less likely show CPP males, but age behavior observed. Conditioning increased number D2 + co-labelled adults not adolescents. D1:D2 ratio also sex- age-dependently changed saline. These findings suggest aversion unlikely an explanation for vulnerability use. Sex- age-specific expressions D1 injections, which has implications subsequent