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

In the present study we investigate, using in vivo microdialysis, the involvement of central 5-HT3 receptors in the effect of dorsal raphe n ucleus (DRN) electrical stimulation on dopamine (DA), 3,4-dihydroxyphe nylacetic acid (DOPAC), and 5-hydroxyindole-3-acetic acid (5-HIAA) ext racellular levels monitored in the nucleus accumbens and the striatum of halothane-anesthetized rats. DRN stimulation (300 mu A, 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 th e ipsilateral striatum at 20 Hz. In both structures DOPAC and 5-HIAA d ialysate contents were enhanced in a frequency-dependent manner. Centr al serotonin (5-HT) depletion, induced by intra-raphe injections of 5, 7-dihydroxytryptamine neurotoxin, abolished the effect of 20 Hz DRN st imulation on DA, DOPAC, and 5-HIAA extracellular levels in both region s. 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-HIAA outflow in both structures. Ondansetron (0.1 and 1 mg/kg) a nd (S)-zacopride (0.1 mg/kg), two 5-HT3 antagonists, significantly imp aired the increase of accumbal DA release induced by 20 Hz DRN stimula tion but did not affect either the decrease of striatal DA release or the increase in DOPAC outflow in both structures. These results indica te that an enhancement of central 5-HT transmission induced by DRN sti mulation differentially affects striatal and accumbal DA release and t hat endogenous 5-HT, via its action on 5-HT3 receptors, exerts a facil itatory control restricted to the mesoaccumbal DA pathway.