Effects of 3,4‐methylenedioxymethamphetamine (MDMA) and d‐methamphetamine on pro‐social behavior in drug‐naïve female nonhuman primates

Abstract

Previous preclinical studies have demonstrated that 3,4‐methylenedioxymethamphetamine (MDMA) dose‐dependently increases pro‐social behavior and affiliative vocalizations in male nonhuman primates. As diagnostic criteria for several psychiatric diseases includes deficits in social functioning, examining the conditions under which MDMA selectively increases pro‐social behavior may provide important insights into MDMA's potential as a therapeutic. One such condition is whether a subject's drug history has any impact on MDMA's ability to modulate social behavior. Here, we examined the ability of MDMA and d‐methamphetamine (MA) to modulate pro‐social behavior and affiliative vocalizations in four pairs of drug‐naïve female squirrel monkeys (n=8). Doses of MDMA (0.1‐1.0 mg/kg), MA (0.03‐0.3 mg/kg) or saline vehicle were administered 10‐min prior to observation sessions in which pro‐social behavior (huddling, touching, and sitting within proximity to each other) was scored by a blind observer. Vocalizations were recorded and spectrograph analyses were used to characterize vocalizations as either affiliative or aggressive. Results show that MDMA dose‐dependently increased pro‐social behavior, with 1.0 mg/kg eliciting the highest pro‐social scores in comparison to saline, whereas the dopamine‐preferring releaser MA elicited little pro‐social behavior in comparison to saline. In contrast, both MDMA and MA dose‐dependently decreased all measures of vocalizations in females, with the highest total number of vocalizations evident after 0.1 mg/kg MDMA and the lowest total number of vocalizations evident at 1.0 mg/kg MDMA. Aggressive vocalizations were not elicited by either MDMA or MA. These results corroborate previous findings that MDMA, but not d‐MA, increases pro‐social behavior in male subjects and extends them to females. However, MDMA's increase in pro‐social behavior appears to be de‐coupled from vocalizations in drug‐naïve female subjects. These data are in contrast to other reports in male subjects with drug histories showing that MDMA dose‐dependently increases affiliative behavior and vocalizations. Taken together, these results suggest that sex and drug‐history may be important variables in considering MDMA's efficacy in increasing pro‐social behavior. Future studies will include drug naïve male subjects to investigate sex as a biological variable as well as other drugs that vary in selectivity for dopamine or serotonin release.