(±)-3,4-Methylenedioxymethamphetamine-induced changes in the basal activity and pharmacological responsiveness of nigrostriatal dopamine neurons

Abstract

The present study examined the effects of methylenedioxymethamphetamine (MDMA) on the basal activity and pharmacological responsiveness of rat nigrostriatal dopamine (DA) neurons. Under standard in vivo extracellular single-unit recording conditions, acute MDMA administered alone (i.v.) inhibited the firing rate of nigrostriatal DA neurons in a dose-dependent fashion. The potency of MDMA to elicit this inhibition was significantly reduced following depletion of either serotonin or DA. Acute MDMA pretreatments (10 mg/kg i.v., 90 s) also profoundly enhanced the sensitivity of nigrostriatal DA neurons to the rate-inhibitory effects of the D-2 DA receptor agonist quinpirole but not apomorphine. It has previously been demonstrated that the ability of quinpirole and apomorphine to inhibit nigrostriatal DA neuronal activity is dependent on the basal firing rate of the cell. Both acute MDMA and a single dose of MDMA (15 mg/kg i.p.) one week prior eliminated the rate dependency of quinripole- and apomorphine-induced inhibition of the firing rate of these cells. These data suggest that, although MDMA is known to be a serotonergic neurotoxin, this compound may also exert direct functional effects on the nigrostriatal DA system.