Dopamine D-2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin

INTRACEREBROVENTRICULAR (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D-2 receptors measured with [H-3]raclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (+/-)-7-hydroxy-dipropyl-amino-tetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D-2 receptor increase comprises receptors localized both post-and presynaptically. The density of striatal DA D-1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D-2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.