Examination of the action of 3,4-methylenedioxymethamphetamine on rat A10 dopamine neurons

Abstract

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 an 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 α‐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. © 1996 Wiley‐Liss, Inc.

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…Therefore, the resultant interaction between DA and 5-HT on specific receptors accounts for most of its subjective effects (Bankson and Cunningham 2001;Gold et al 1988;Liechti and Vollenweider 2001). With regard to the functions of MDMA on the dopaminergic neurons, it has been shown that MDMA inhibits the firing rate of ventral tegmental area cells (Gifford et al 1996;Kelland et al 1989;Matthews et al 1989; but see Piercey et al 1990). Despite the fact that this inhibition is caused by DA receptor-dependent mechanisms (Gifford et al 1996;White et al 1996), no detailed information is available yet on the membrane processes involved.…”

“…This is clearly supported by the blocking effects obtained with the specific D2 receptor antagonist sulpiride. In agreement with these data, 1) inhibitory effects of MDMA, mediated by DA receptors, have been already described on VTA DAergic cells recorded in vivo (Gifford et al 1996;White et al 1996); 2) the systemic injection of MDMA elevates extracellular DA in the substantia nigra (Yamamoto et al 1995).…”

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…Therefore, the resultant interaction between DA and 5-HT on specific receptors accounts for most of its subjective effects (Bankson and Cunningham 2001;Gold et al 1988;Liechti and Vollenweider 2001). With regard to the functions of MDMA on the dopaminergic neurons, it has been shown that MDMA inhibits the firing rate of ventral tegmental area cells (Gifford et al 1996;Kelland et al 1989;Matthews et al 1989; but see Piercey et al 1990). Despite the fact that this inhibition is caused by DA receptor-dependent mechanisms (Gifford et al 1996;White et al 1996), no detailed information is available yet on the membrane processes involved.…”

“…This is clearly supported by the blocking effects obtained with the specific D2 receptor antagonist sulpiride. In agreement with these data, 1) inhibitory effects of MDMA, mediated by DA receptors, have been already described on VTA DAergic cells recorded in vivo (Gifford et al 1996;White et al 1996); 2) the systemic injection of MDMA elevates extracellular DA in the substantia nigra (Yamamoto et al 1995).…”

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…Therefore, the resultant interaction between DA and 5-HT on specific receptors accounts for most of its subjective effects (Bankson and Cunningham 2001;Gold et al 1988;Liechti and Vollenweider 2001). With regard to the functions of MDMA on the dopaminergic neurons, it has been shown that MDMA inhibits the firing rate of ventral tegmental area cells (Gifford et al 1996;Kelland et al 1989;Matthews et al 1989; but see Piercey et al 1990). Despite the fact that this inhibition is caused by DA receptor-dependent mechanisms (Gifford et al 1996;White et al 1996), no detailed information is available yet on the membrane processes involved.…”

“…This is clearly supported by the blocking effects obtained with the specific D2 receptor antagonist sulpiride. In agreement with these data, 1) inhibitory effects of MDMA, mediated by DA receptors, have been already described on VTA DAergic cells recorded in vivo (Gifford et al 1996;White et al 1996); 2) the systemic injection of MDMA elevates extracellular DA in the substantia nigra (Yamamoto et al 1995).…”

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…Therefore, the resultant interaction between DA and 5-HT on specific receptors accounts for most of its subjective effects (Bankson and Cunningham 2001;Gold et al 1988;Liechti and Vollenweider 2001). With regard to the functions of MDMA on the dopaminergic neurons, it has been shown that MDMA inhibits the firing rate of ventral tegmental area cells (Gifford et al 1996;Kelland et al 1989;Matthews et al 1989; but see Piercey et al 1990). Despite the fact that this inhibition is caused by DA receptor-dependent mechanisms (Gifford et al 1996;White et al 1996), no detailed information is available yet on the membrane processes involved.…”

“…This is clearly supported by the blocking effects obtained with the specific D2 receptor antagonist sulpiride. In agreement with these data, 1) inhibitory effects of MDMA, mediated by DA receptors, have been already described on VTA DAergic cells recorded in vivo (Gifford et al 1996;White et al 1996); 2) the systemic injection of MDMA elevates extracellular DA in the substantia nigra (Yamamoto et al 1995).…”