BLOCKADE OF STRIATAL 5-HYDROXYTRYPTAMINE(2) RECEPTORS REDUCES THE INCREASE IN EXTRACELLULAR CONCENTRATIONS OF DOPAMINE PRODUCED BY THE AMPHETAMINE ANALOG 3,4-METHYLENEDIOXYMETHAMPHETAMINE

5-Hydroxytryptamine, (5-HT2) receptor antagonists have been shown to i nterfere with the stimulation of striatal dopamine synthesis and relea se produced by the amphetamine analogue 3,4-methylenedioxymethamphetam ine (MDMA). To localize the receptors responsible for the attenuation of MDMA-induced release, 5-HT2 receptor antagonists were infused via t he microdialysis probe directly into the brains of awake, freely movin g rats before the systemic administration of MDMA. Intrastriatal infus ions of the selective 5-HT2 antagonist MDL 100,907 produced a concentr ation-dependent inhibition of MDMA-induced dopamine release. Similar r esults were observed with intrastriatal infusions of the 5-HT2 antagon ist amperozide. In contrast, infusion of MDL 100,907 into the midbrain region near the dopaminergic cell bodies was without effect on the MD MA-induced elevation of extracellular dopamine in the ipsilateral stri atum. Neither antagonist attenuated basal transmitter efflux nor the M DMA-stimulated release of [H-3]dopamine from striatal slices in vitro indicating that the in vivo effect of the antagonists was not due to i nhibition of the dopamine uptake carrier. Intrastriatal infusion of te trodotoxin reduced both basal and MDMA-stimulated dopamine efflux and eliminated the effect of intrastriatal MDL 100,907. The results indica te that 5-HT2 receptors located in the striatum augment the release of dopamine produced by high doses of MDMA. Furthermore, these 5-HT2 rec eptors appear to be located on nondopaminergic elements of the striatu m.