Opposite change of in vivo dopamine release in the rat nucleus accumbens and striatum that follows electrical stimulation of dorsal raphe nucleus: Role of 5-HT3 receptors

Abstract

In the present study we investigate, using in vivo microdialysis, the involvement of central 5-HT3 receptors in the effect of dorsal raphe nucleus (DRN) electrical stimulation on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA) extracellular levels monitored in the nucleus accumbens and the striatum of halothane- anesthetized rats. DRN stimulation (300 μA, 1 msec at 3, 5, 10, and 20 Hz for 15 min) induced a frequency-dependent increase of accumbal DA release and a concomitant reduction of DA release in the ipsilateral striatum at 20 Hz. In both structures DOPAC and 5-H1AA dialysate contents were enhanced in a frequency-dependent manner. Central serotonin (5-HT) depletion, induced by intra-raphe injections of 5,7-dihydroxytryptamine neurotoxin, abolished the effect of 20 Hz DRN stimulation on DA, DOPAC, and 5-H1AA extracellular levels in both regions. The 5-HT synthesis inhibitor parachlorophenylalanine (3 X 400 mg/kg, i.p., for 3 d), although preventing the effect on DA release, failed to modify significantly the effect of 20 Hz DRN stimulation on DOPAC and 5-H1AA outflow in both structures. Ondansetron (0.1 and 1 mg/kg) and (S)- zacopride (0.1 mg/kg), two 5-HT3 antagonists, significantly impaired the increase of accumbal DA release induced by 20 Hz DRN stimulation but did not affect either the decrease of striatal DA release or the increase in DOPAC outflow in both structures. These results indicate that an enhancement of central 5-HT transmission induced by DRN stimulation differentially affects striatal and accumbal DA release and that endogenous 5-HT, via its action on 5-HT3 receptors, exerts a facilitatory control restricted to the mesoaccumbal DA pathway.