BLOCKADE OF STRIATAL 5-HYDROXYTRYPTAMINE(2) RECEPTORS REDUCES THE INCREASE IN EXTRACELLULAR CONCENTRATIONS OF DOPAMINE PRODUCED BY THE AMPHETAMINE ANALOG 3,4-METHYLENEDIOXYMETHAMPHETAMINE
Cj. Schmidt et al., BLOCKADE OF STRIATAL 5-HYDROXYTRYPTAMINE(2) RECEPTORS REDUCES THE INCREASE IN EXTRACELLULAR CONCENTRATIONS OF DOPAMINE PRODUCED BY THE AMPHETAMINE ANALOG 3,4-METHYLENEDIOXYMETHAMPHETAMINE, Journal of neurochemistry, 62(4), 1994, pp. 1382-1389
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.