Effects of acute,subchronic and intermittent MDMA (‘ECSTASY’) administration on agonistic interactions between male mice

Recent studies suggest that acute administration of 3,4‐methylenedioxymethamphetamine (MDMA), an amphetamine derivative popularly known as “ecstasy,” produces an antiaggressive effect in male mice. However, there is no evidence with respect to the development of tolerance or sensitization after its subchronic or intermittent administration. In this study, we examined the action of low to moderate doses of MDMA (1.25, 2.5 and 5 mg/kg, i.p), administered acutely, subchronically (for 7 days) or intermittently, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after the drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with MDMA provoked a significant reduction of aggressive behaviors, without altering immobility. However, this action was only selective at 1.25 mg/kg. With the intermediate (2.5 mg/kg) and the highest doses (5 mg/kg) of the drug, it was observed a significant decrease of offensive behaviors, accompanied by an increase of exploration from a distance, avoidance/flee and defense/submission behaviors. This ethopharmacological profile could indicate the existence of an anxiogenic‐like effect of MDMA. The overall picture of the effects of MDMA was very similar in the acutely, intermittently and daily treated animals. No tolerance or sensitization to the actions of the drug was developed after its repeated or intermittent administration.