Role of serotonin2A and serotonin2B/2C receptor subtypes in the control of accumbal and striatal dopamine release elicited in vivo by dorsal raphe nucleus electrical stimulation

This study investigates, using in vivo microdialysis, the role of serotonin(2A) (5-HT2A) and 5-HT2B/2C receptors in the effect of dorsal raphe nucleus (DRN) electrical stimulation on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) extracellular levels monitored in the nucleus accumbens (NAC) and the striatum of halothane-anesthetized rats. Following DRN stimulation (300 mu A, 1 ms, 20 Hz, 15 min) DA release was enhanced in the NAC and reduced in the striatum. The 5-HT2A antagonist SR 46349B (0.5 mg/kg) and the mixed 5-HT2A/2B/2C antagonist ritanserin (0.63 mg/kg) significantly reduced the effect of DRN stimulation on DA release in the NAC but not in the striatum. DA responses to DRN stimulation were not affected by the 5-HT2B/2C antagonist SE 206553 (5 mg/kg) in either region. None of these compounds was able to modify the enhancement of DOPAC and 5-HIAA outflow induced by DRN stimulation in either the NAC or the striatum, Finally, in both brain regions basal DA release was significantly increased only by SE 206553, These results indicate that 5-HT2A but not 5-HT2B/2C receptors participate in the facilitatory control exerted by endogenous 5-HT on accumbal DA release. Conversely, 5-HT2B/2C receptors tonically inhibit basal DA release in both brain regions.