Rats exposed to MDMA on postnatal days 11–20 showed consistent impairments in spatial learning and memory in the Morris water maze when tested on that maze first, with longer latencies, longer path lengths, and greater cumulative distance from the goal compared to saline controls. On probe trials, MDMA-treated animals that received the water maze first had increased distance from the target site. No MDMA effects were observed on cued trials, straight channel swimming, or working memory, indicating the drug did not impair swimming ability or basic task skills. No MDMA effects were found on the Barnes maze, though interpretation was limited by poor performance on that task.
MDMA damages fine serotonergic fibers and nerve terminals in adult organisms, while developing animals appear less susceptible, possibly due to a lack of drug-induced hyperthermia. In neonatal rats given MDMA from postnatal days 1–4, hyperthermia was produced in some groups, but all effects were independent of body temperature. The hippocampus showed significant reductions in serotonergic markers at postnatal days 25 and 60, but no effect at 9 months. However, reduced fiber density occurred in two neocortical areas, and hyperinnervation appeared in the caudate-putamen and nucleus accumbens shell. MDMA also caused a two-fold increase in cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus, indicating apoptotic cell death and long-term reorganization of forebrain serotonergic innervation. Offspring of MDMA-using women may face heightened risk for abnormal neural and behavioral development.