Regulation of striatal dopamine release through 5-HT1 and 5-HT2 receptors

Abstract

Dopamine (DA) release in the striatum is regulated by 5- hydroxytryptamine (5-HT, serotonin) through putative heteroreceptors. However, the effect of 5-HT is controversial. The present study investigated the effects of different 5-HT receptor ligands on DA release in the rat striatum by using in vivo microdialysis in conscious and freely moving rats. Perfusion with 5-carboxamidotryptamine, anpirtoline, pindobind-5-HT(1A), and isamoltane demonstrated the involvement of 5-HT(1A) and 5-HT(1B) receptors in facilitating DA release. In contrast, 5-HT2 receptors mediated inhibition of DA efflux, as shown by experiments with DOI [R-(-)-1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane] and ketanserin. A 5-HT3 agonist (1-(m- chlorophenyl)-biguanide hydrochloride) did not have any effect. None of the agonists used affected DA uptake into striatal synaptosomes. Unilateral 6- hydroxydopamine lesioning of the nigrostriatal DA pathway led to a selective decrease in 5-HT2 receptors. It is concluded that there are 5-HT2 heteroreceptors at the dopaminergic terminals that mediate inhibition of DA release. Further investigation is required to clarify the localization of the 5-HT1 receptors in the striatum.