BLOCKADE OF A RESTING POTASSIUM CHANNEL AND MODULATION OF SYNAPTIC TRANSMISSION BY ECSTASY IN THE HIPPOCAMPUS

3,4-Methylenedioxymethamphetamine (ecstasy, MDMA) and related amphetam ines are CNS stimulants that have euphoric, memory-enhancing and neuro toxic properties. When applied in pharmacological doses to cultured ra t hippocampal neurons, ecstasy reduced the conductance of a 50-pS bari um-sensitive resting K+ channel and increased neuronal excitability. E cstasy enhanced synaptic strength by irreversibly increasing the ampli tude of excitatory autaptic currents and the frequency of spontaneous excitatory postsynaptic currents. Ecstasy did not alter the amplitude of inhibitory autaptic currents or the frequency of spontaneous inhibi tory postsynaptic currents but reversibly prolonged the decay phase of inhibitory autaptic currents and spontaneous inhibitory postsynaptic currents. These results suggest that K+ channel blockade and the effec ts on synaptic transmission may contribute to the;pharmacological effe cts of ecstasy acid other amphetamines.