Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat.

Abstract

The effects of microinfusing L-glutamate, serotonin (5-HT), (+-)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT; a 5-HT1A agonist), and muscimol (a GABAA agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT, dopamine (DA) and their metabolites in the nucleus accumbens were studied in unanesthetized, freely moving, adult male Wistar rats, using the technique of microdialysis coupled with small-bore HPLC. Administration of 0.75 micrograms L-glutamate produced a 25-50% increase (P less than 0.05) in the extracellular levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a lesser extent, 5-HT produced a significant (P less than 0.05) decrease in the extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 microgram) had little effect on the extracellular concentrations of 5-HT or DA following its administration. In general, the extracellular levels of the major metabolites of 5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid receptors and inhibited by stimulation of 5-HT1A autoreceptors, and (b) the dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area DA projection to the nucleus accumbens.