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 (12.5mg/kg i.p., once a week, per three weeks), serotonergic deficit was evident in hippocampal slices as 56.3% reduction in 5-HT content (p=0.04) 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%; n=12 vs. 29.2 ± 3.2%; n=12; p<0.01). Non-neurotoxic dose of MDMA (12.5 mg/kg, 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.
Morini
Raffaella
R
Department of Preclinical and Clinical Pharmacology Mario Aiazzi-Mancini, University of Florence, Florence, Italy.
Mlinar
Boris
B
Baccini
Gilda
G
Corradetti
Renato
R
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D006213:Hallucinogens / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007858:Learning / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D012701:Serotonin / Q000032:analysis; D013997:Time Factors
D006213:Hallucinogens; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine