MK-801 potentiates the acute neuroendocrine and behavioural effects of 3,4-methylenedioxymethamphetamine

3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') causes the release of 5-HT from serotonergic nerve terminals and subsequent degeneration of serotonergic neurons in the brains of rats and non-human primates. MK-801 is a non-competitive NMDA receptor antagonist which has recently been shown to be neuroprotective against long-term MDMA-induced neurotoxicity. In the present study, the effects of pretreatment with MK-801 on the acute neurochemical, neuroendocrine and behavioural responses to MDMA were examined in a test design which allowed serial blood samples to be obtained whilst continuous home cage activity was monitored over a six hour period. MDMA caused significant reductions in concentrations of 5HT and 5HIAA in both the hypothalamus and the frontal cortex, a response which was unaffected by pretreatment with MK-801. However, the characteristic hyperactivity induced by administration of MDMA was significantly potentiated by MK-801 as were MDMA-induced increases in the secretion of both prolactin and corticosterone. Thus it is concluded that although MK-801 is capable of protecting against the long term neurotoxic effects of MDMA it does not protect against the acute effects of this drug.