Use of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has increased dramatically in recent years, yet little is known about its effects on the developing brain. Neonatal rats were administered MDMA on days 1-10 or 11-20 (analogous to early and late human third trimester brain development). MDMA exposure had no effect on survival but did affect body weight gain during treatment. After treatment, body weight largely recovered to 90-95% of controls. MDMA exposure on days 11-20 resulted in dose-related impairments of sequential learning and spatial learning and memory, whereas neonatal rats exposed on days 1-10 showed almost no effects. At neither stage of exposure did MDMA-treated offspring show effects on swimming ability or cued learning. Brain region-specific dopamine, serotonin, and norepinephrine changes were small and were not correlated to learning changes. These findings suggest that MDMA may pose a previously unrecognized risk to the developing brain by inducing long-term deleterious effects on learning and memory.

The effects of neonatal d-methamphetamine (MA) treatment on cued and spatial learning and memory were investigated. MA was administered to neonatal rats on postnatal days 11-20. All groups received four subcutaneous injections per day. Group MA40-4 received 40 mg. kg(-1). d(-1) of MA in four divided doses (10 mg/kg per injection). Group MA40-2 received 40 mg. kg(-1). d(-1) of MA in two divided (20 mg/kg/injection) and saline for the other two injections per day. Controls received saline for four injections per day. As adults, both MA groups showed no differences in swimming ability in a straight swimming channel. The MA40-4 group showed no differences in cued learning, but was impaired in hidden platform learning in the Morris water maze on acquisition. They also showed reduced memory performance on probe trials. Similar trends were seen on reversal learning and reversal probe trials. Reduced platform-size learning trials caused spatial learning impairments to re-emerge in the MA40-4 group. The MA40-2 group showed no differences in straight channel swimming, but was slower at finding the visible platform during cued learning. They were also impaired during acquisition and memory trials in the Morris hidden platform maze. They showed a similar trend on reversal learning and memory trials, but were not different during reduced platform-size learning trials. When the MA40-2 group's performance on hidden platform learning and memory trials was adjusted for cued trial performance, the spatial learning deficits remained. Deficits of spatial learning and memory are a selective effect of neonatal methamphetamine treatment irrespective of other learning and performance variables.

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