EXAMINATION OF THE ACTION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE ON RATA10 DOPAMINE NEURONS

Extracellular single cell recording was used to examine the effect of intravenous administration of (-), (+), and(+)-3,4-methylenedioxymetha mphetamine (MDMA) on A10 dopamine (DA) neurons in chloral hydrate anes thetized male rats. Both (+/-)-MDMA and (+)-MDMA inhibited the firing rate of most (79%) A10 DA cells. By contrast, (-)-MDMA induced either no effect or a slight increase in the firing rate of these cells. Anal ysis of the effects of (+/-)-MDMA on the firing pattern of the DA cell s revealed an overall decrease in the percentage of spikes in bursts b ut both increases and decreases were seen in the coefficient of variat ion of interspike intervals. To determine the contribution of 5-HT and DA to the (+/-)-MDMA-induced inhibition of A10 DA cells rats were pre treated either with the 5-HT synthesis inhibitor-p-chlorophenylalanine (PCPA) or the DA synthesis inhibitor alpha-methyl-p-tyrosine (AMPT). Pretreatment of rats with PCPA did not reduce the ability of (+/-)-MDM A to inhibit the DA cells. However, in rats pretreated with AMPT, the (+/-)-MDMA-induced inhibition was blocked and some cells (44%) showed instead an increase in firing rate following administration of (+/-)-M DMA. The administration of l-3,4-dihydroxyphenylalanine (L-DOPA) to AM PT-treated rats rapidly restored the inhibition of cell firing by (+/- )-MDMA. In conclusion, the results reported here demonstrate that MDMA has an overall inhibitory effect on A10 DA cells. Despite MDMA's grea ter potency in releasing 5-HT compared to DA, the inhibitory effect of this drug on A10 DA cells appears to be mediated by the latter transm itter. (C) 1996 Wiley-Liss, Inc.