Examination of the action of 3,4-methylenedioxymethamphetamine on rat A10 dopamine neurons.
Extracellular single cell recording was used to examine the effect of intravenous administration of (-), (+), and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) on A10 dopamine (DA) neurons in chloral hydrate anesthetized 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. Analysis of the effects of (+/-)-MDMA on the firing pattern of the DA cells revealed on overall decrease in the percentage of spikes in bursts but both increases and decreases were seen in the coefficient of variation of interspike intervals. To determine the contribution of 5-HT and DA to the (+/-)-MDMA-induced inhibition of A10 DA cells rats were pretreated 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 (+/-)-MDMA 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 (+/-)-MDMA. The administration of l-3,4-dihydroxyphenylalanine (L-DOPA) to AMPT-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 greater 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 transmitter.
Gifford
A N
AN
Medical Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Minabe
Y
Y
Toor
A
A
Wang
R Y
RY
Ashby
C R
CR
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000187:drug effects*
D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine