High-dose MDMA does not result in long-term changes in impulsivity in the rat

Rationale Evidence suggests that recreational users of (±)3,4-methylenedioxymethamphetamine HCl (MDMA, “ecstasy”) have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.Objective We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.Methods Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n=24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.Results There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7–8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363±14 ng/g and control 440±10 ng/g tissue).Conclusion These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.