Anxiogenic activity of methylenedioxymethamphetamine (Ecstasy): An experimental study

Methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy, is widely abused as a recreational agent. Reports of death following MDMA intake has aroused serious concern. Although some of the clinical symptoms of MDMA toxicity include severe anxiety, panic, excitation and agitation, behavioural studies on the drug are sparse and incomplete. The present study investigated the anxiogenic activity of MDMA in rats, using yohimbine (2 mg/kg, i.p.) as the standard anxiogenic agent for comparison. The experimental methods used were the open-field, elevated plus-maze, social interaction and novelty-suppressed feeding latency tests, all the tests being experimentally validated as rodent models of clinical anxiety. In addition, the effect of MDMA was assessed on rat brain tribulin activity in terms of endogenous monoamine oxidase (MAO) A and B inhibition. Tribulin has been postulated to function as an endogenous marker of anxiety. MDMA (5 and 10 mg/kg i.p.) reduced ambulation and rears, and increased immobility and defaecation, in the open-field test. These doses of MDMA produced a dose-related decrease in the number of entries and time spent on the open arms of the elevated plus maze, reduced social interaction in paired rats and increased the feeding latency time in an unfamiliar environment in food deprived rats. A qualitatively similar response was induced by yohimbine in all these test parameters. Both MDMA (5 and 10 mg/kg, i.p.) and yohimbine (2 mg/kg, i.p.) increased rat brain tribulin activity, the increase in the MAO A inhibitor component being more than that on the MAO B inhibitor component. Several anxiogenic agents induce a similar response, as does anxiety associated with addictive drug withdrawal. The anxiogenic effects of MDMA and yohimbine on the elevated plus maze were inhibited by the benzodiazepine anxiolytic lorazepam (0.25 mg/kg, i.p.). However, the 5-HT(1A) receptor agonist-antagonist, buspirone (2.5 mg/kg, i.p.), selectively inhibited the anxiogenic effect of MDMA. Earlier studies have indicated that MDMA has significant effect on rat brain 5-HT(1A) receptors and induces an increase in serotonergic activity in this species. The results of the present study indicate that MDMA induces significant anxiogenic response in rats which may involve the serotonergic neurotransmitter system.