Effects of para-methoxyamphetamine (PMA) on agonistic encounters between male mice

Para-methoxyamphetamine (PMA) is a synthetic drug chemically similar to the recreational drug 3,4-methylenedioxy-methamphetamine (MDMA or “ecstasy”) and often replaces MDMA in tablets that show an “ecstasy” logo. PMA displays a higher toxic potential than MDMA, but the behavioral profile of PMA has been scarcely studied in animal models. Here we evaluated the effects of PMA (2, 4, 8, and 12 mg/kg, i.p.) on agonist encounters between male mice using an ethopharmacological approach, the isolation-induced aggression model. Likewise, since PMA and MDMA share common mechanisms of action, we compared the behavioral profile of PMA with that induced by MDMA (8 mg/kg, i.p.) which behavioral effects in this model are well characterized. Individually housed mice were exposed to anosmic standard opponents 30 min after drug administration. The encounters were videotaped and evaluated using an ethologically based analysis. PMA (all doses) significantly reduced offensive behaviors (threat and attack), however, a detailed behavioral analysis suggests that the observed antiaggressive effect seems to be unspecific, showing a complex dose-dependent behavioral profile. Thus, antiaggresive actions observed after the administration of the lowest dose were accompanied by increases in social investigation, avoidance/flee behaviors and non-social explorations, together with a reduction of digging behavior. This pattern reflects both approach-contact behaviors and avoidance-flee behaviors. From 4 mg/kg to 12 mg/kg, the increase in social investigation previously observed disappears, and there is a slight increase in immobility, together with a different behavioral pattern that suggests anxiogenic effects of PMA, similar to those reported after the administration of MDMA. The higher doses of PMA exhibit a behavioral profile very similar to that observed in animals treated with MDMA, with the exception of the immobility produced by PMA. These findings show for the first time the non-specific antiaggressive profile of PMA in the model of aggression induced by isolation in male mice.