Braida D, Pozzi M, Cavallini R, Sala M (2002). 3,4 methylenedioxymethamphetamine (ecstasy) impairs eight-arm radial maze performance and arm entry pattern in rats. Behav Neurosci 116: 298-304
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Performance on the 8-arm radial maze was compared in rats given saline and rats given 1, 2, or 3 mg/kg MDMA, with all doses selected on the basis of a study determining degree of MDMA-stimulated activity. None of the doses are known for producing neurotoxicity in rats. The dose-determination study found that 4 mg/kg MDMA produced markedly increased locomotor activity, as assessed via photobeam crossings, and increased observer-scored stereotypy (such as repetitive sniffing or rearing). (The 8-arm radial maze consists of a central entry point and food-baited arms, and rats are expected to enter baited arms and avoid arms they have already entered.) After 10 to 30 days of training, rats were tested with the radial maze 20 min after saline/MDMA injection, and performance was evaluated for total number of errors, total number of correct choices before 1st error, and number of rats per condition making more than 1 error per trial ("amnesic rats"). Preferred angle between consecutive area entries was also measured, noting that pre-drug and saline rats prefered a 45 degree angle (adjacent entry). Radial maze performance was unaffected at 1 mg/kg and 2 mg/kg MDMA. While rats given 3 mg/kg MDMA made a similar number of errors and similar number of correct choices before errors, a greater number of rats receiving 3 mg/kg made more than 1 error. Rats given 3 mg/kg also showed less of a preference for 45 degree angle of entry, and instead exhibited a rightward shift in distribution of preferred angle of entry. In a second study, the same procedures were used except that a 2-h delay separated the fourth and fifth choice in the task, and with assessment performed on 3 consecutive days. (Data was analyzed as pre-delay and post-delay). While rats in all conditions performed worse post-delay than pre-delay, rats given 3 mg/kg made more errors and had higher error rates than rats given saline, 1 mg/kg or 2 mg/kg MDMA. At pre-delay, only rats given 3 mg/kg deviated from preference for 45 degree angle for consecutive arm entry, with preference for 90 degree angle increasing. However, rats given 2 and 3 mg/kg showed less preference for 45 degree arm entry at post-delay. Taken together, these research findings indicate that MDMA acutely affects either long-term working memory or visual-spatial skills at doses that failed to produce hyperactivity. Doses that were found not to produce hyperactivity are similar to doses taken by ecstasy users, suggesting that humans may experience similar effects on working memory. In contrast, doses that produce hyperactivity are probably only equivalent to very high doses in humans, and the effects seen at these doses probably do not represent what would be expected for a typical human dose of ecstasy or MDMA. The neurotransmitter systems and receptors found to control hyperactivity (e.g. Bankson and Cunningham 2002) are not necessarily involved in producing acute effects at doses usually consumed by humans. It is unclear how to relate radial maze performance to some of the tasks tested in humans, such as Stroop task (Vollenweider et al. 1998), visual search (Gamma et al. 2000) or digit-symbol substitution (Cami et al. 2000).

 
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