The effects of acute and sub-chronic MDMA were assessed using a procedure designed to test rodent working memory capacity: the odor span task (OST). Rats were trained to select an odor that they had not previously encountered within the current session, and the number of odors to remember was incremented up to 24 during the course of each session. In order to separate drug effects on the OST from more general performance impairment, a simple olfactory discrimination was also assessed in each session. In Experiment 1, acute doses of MDMA were administered prior to select sessions. MDMA impaired memory span in a dose-dependent fashion, but impairment was seen only at doses (1.8 and 3.0 mg/kg) that also increased response omissions on both the simple discrimination and the OST. In Experiment 2, a sub-chronic regimen of MDMA (10.0 mg/kg, twice daily over four days) was administered after OST training. There was no evidence of reduced memory span following sub-chronic MDMA, but a temporary increase in omission errors on the OST was observed. In addition, rats exposed to sub-chronic MDMA showed delayed learning when the simple discrimination was reversed. Overall, the disruptive effects of both acute and sub-chronic MDMA appeared to be due to non-mnemonic processes, rather than effects on specific memory functions.
Research with recreational ecstasy users has revealed deficits on a number of cognitive tasks. A history of heavy ecstasy use is associated with impaired performance on tests of attention, learning and working memory with simple cognitive tasks (e.g., reaction time) often unaffected, and more complex tasks involving higher processing loads more severely affected (Montgomery and Fisk, 2008, Murphy et al., 2009, Nulsen et al., 2010 and Parrott, 2013). Of course, these studies have many limitations including the accuracy of the self-reported drug histories on which they are based and the complication that most ecstasy users are also multiple drug users. Further, pills believed by users to be ecstasy may or may not contain only MDMA (Sherlock, Wolff, Hay, & Conner, 1999). Thus, it is difficult to determine whether the differences between controls and ecstasy users are actually based on MDMA use. Indeed, when groups of ecstasy users are compared with groups of participants who do not use ecstasy, but are matched with respect to use of marijuana or other drugs, several studies have found comparable cognitive deficits (e.g., Croft et al., 2001, Dafters et al., 2004 and de Sola et al., 2008), although others have found more severe deficits in ecstasy users (Daumann et al., 2005 and Nulsen et al., 2010). Due to these difficulties in interpretation and given the ethical restrictions associated with administering MDMA to humans, preclinical studies using non-human subjects, particularly rodents, have an important role in the investigation of these cognitive disruptions.
