Morley KC, Gallate JE, Hunt GE, Mallet PE, McGregor IS (2001). Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine ("Ecstasy"). Eur J Pharmacol 433: 91-9.
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Performance on the emergence test, elevated plus maze, social interaction and novel object recognition tests were compared across groups of rats given vehicle, MDMA or d-amphetamine, with MDMA given in high or moderate doses. 5 mg/kg MDMA was either administered every 4 h at least 3 times on 2 consecutive days (high dose), or 1 dose of 5 mg/kg followed 2 vehicle injections every 4 h on 2 consecutive days (low dose). D-amphetamine was administered in 4 1mg/kg doses every 4 h on 2 consecutive days Social interaction involved pairs of unacquainted rats who had received the same drug treatment, and novel object recognition scored as percent time exploring novel versus familiar object. All comparisons were made 12 wks (3 months) after MDMA or vehicle administration. Rats in the high MDMA group took longer to emerge from a hide box, emerged less frequently, spent less time in the open field and spent less time rearing than amphetamine-treated or control rats. Risk taking remained the same. Rats in the moderate MDMA group emerged from hide box less frequently than did controls. When compared on the elevated plus maze, both rats who received the high and the moderate doses of MDMA spent more time in the closed arms, spent less time in the open arms and made fewer open-arm entries than did either amphetamine-treated or vehicle-treated rats. In the social interaction test, rats who received a high dose of MDMA had decreased total social interaction time, fewer social interactions, decreased movement across space, decreased time spent rearing relative to the vehicle-treated (but not amphetamine-treated) rats. High-dose MDMA rats had decreased time spent in social interaction compared with amphetamine-treated controls. Rats who received a moderate dose of MDMA had shorter-duration social interactions than vehicle-treated rats. After 15 minute delay, but not after 60 minute delay, rats given high dose MDMA spent less time exploring novel object than vehicle-treated or amphetamine-treated rats. While moderate-dose MDMA rats spent less time exploring the novel object than either vehicle or amphetamine-treated rats after either 15 or 60 minute delay, this difference was not significant. These findings suggest that a moderate or high dose of MDMA increased anxiety-related behaviors and decreased behaviors associated with reduced anxiety, and a high dose of MDMA impaired memory for familiar objects. Neurochemical analyses of serotonergic or other brain areas were not performed after assessing behavior. Compare these findings with those of Mechan et al, 2002, finding reduced anxiety on several measures, including elevated plus maze, in Dark Agouti rats. Note also that decreased social interaction was also found in adolescent rats from a different strain.