Microdialysis studies on 3,4-methylenedioxymethamphetamine-induced dopamine release: effect of dopamine uptake inhibitors

Abstract

The effect of dopamine (DA) and serotonin (5-HT) uptake inhibitors on 3,4-methylenedioxymethamphetamine (MDMA)-induced increase in DA efflux was studied using in vivo microdialysis. MDMA was infused directly into the anterolateral striatum via the dialysis probe. The local administration of MDMA produced a dose- and time-dependent increase in the extracellular concentration of DA in the striatum. Peripheral administration of the DA uptake blockers, mazindol (5 mg/kg, i.p.) or GBR 12909 (10 mg/kg, i.p.), produced a slight but significant increase in the extracellular concentration of DA. Moreover, pretreatment with either mazindol or GBR 12909 30 min before the infusion of MDMA (10 microM) significantly attenuated the MDMA-induced increase in the extracellular concentration of DA. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT uptake blocker, 30 min before the infusion of MDMA produced a slight but significant inhibition of MDMA-induced increase in DA concentration. In contrast, pretreatment with the 5-HT2/1C antagonist, ketanserin (3 mg/kg, i.p.), had no significant effect on the increase in DA concentration produced by the local administration of MDMA. These data are suggestive that MDMA increases the concentration of DA in the striatum, in part, via a carrier-mediated mechanism which is largely independent of its effects on 5-HT release.