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The Journal of Neuroscience, August 15, 1998, 18(16):6528-6538

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

Philippe De Deurwaerdère¹, Luis Stinus², and Umberto Spampinato¹

¹ Institut National de la Santé et de la Recherche Médicale Unité 259 and ² Laboratoire Neuropsychobiologie des Désadaptations, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5541, Université Victor Ségalen Bordeaux 2, 33077 Bordeaux Cedex, France

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-HIAA 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-HIAA extracellular levels in both regions. The 5-HT synthesis inhibitor para-chlorophenylalanine (3 × 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) 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.

Key words: microdialysis; nucleus accumbens; striatum; dopamine release; dorsal raphe nucleus; electrical stimulation; serotonin; 5-HT₃ receptors; 5,7-dihydroxytryptamine; para-chlorophenylalanine; halothane-anesthetized rat

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18166528-11$05.00/0

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