Enhanced hippocampal long-term potentiation following repeated MDMA treatment in Dark-Agouti rats.
In rats and primates, (±)3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces both long-lasting damage to serotonergic axons and memory impairment. Our objective was to determine effects of neurotoxic dose of MDMA on long-term potentiation (LTP) in hippocampal area CA1 in Dark-Agouti (DA) rats. One week after neurotoxic MDMA treatment in vivo (12.5mgkg i.p., once a week, per three weeks), serotonergic deficit was evident in hippocampal slices as 56.3% reduction in 5-HT content (p0.04) and as 68.4% reduction in the effect of endogenous 5-HT release on synaptic neurotransmission (p<0.01). In hippocampal slices from the same animals, LTP was on average 46% greater than that observed in sham-treated controls (42.9 ± 3.5% n12 vs. 29.2 ± 3.2% n12 p<0.01). Non-neurotoxic dose of MDMA (12.5 mgkg, i.p., one time) did not change LTP one week after the treatment, suggesting correlation between serotonergic deficit and enhanced synaptic plasticity. We conclude that MDMA-induced impairment of learning and memory is not a consequence of hippocampal LTP inhibition.