EVIDENCE FOR 5-HT4 RECEPTOR SUBTYPE INVOLVEMENT IN THE ENHANCEMENT OFSTRIATAL DOPAMINE RELEASE INDUCED BY SEROTONIN - A MICRODIALYSIS STUDY IN THE HALOTHANE-ANESTHETIZED RAT

The present study, using the in vivo intracerebral microdialysis metho d, investigated the role of different serotonin receptor subtypes in t he control of dopamine (DA) release exerted by serotonin (5-HT) in the striatum of halothane-anesthetized rats. Striatal dialysate DA conten t was reduced following the blockade of voltage-dependent Na+ channels by tetrodotoxin or by the removal of Ca2+ from the perfusion medium, and increased following depolarization with K+ ions. These findings de monstrate that under our experimental conditions, DA content reflects the neuronal origin of the neurotransmitter release. Drugs were locall y applied by means of the microdialysis probe. One, 2.5 and 5 mu M 5-H T significantly enhanced DA release in a concentration-dependent manne r up to 157, 253 and 446% of basal values respectively. The effect ind uced by 1 mu M 5-HT was not blocked by 10 mu M (-)pindolol, a 5-HT1 re ceptor antagonist, 1 mu M ketanserin or 10 mu M cinanserin, both 5-HT2 A antagonists. One or 10 mu M ondansetron (GR 38032F), a selective 5-H T3 antagonist, were also ineffective. In contrast, 10 or 100 mu M DAU 6285, a 5-HT3/4 antagonist, significantly reduced the effect of 5-HT o n DA release (-20% and -60% respectively). Moreover, 100 mu M BIMU 8, a selective 5-HT4 agonist, enhanced DA release (+85%) and this effect was reduced by 100 mu M DAU 6285 (-40%). These results demonstrate tha t in vivo 5-HT exerts a facilitatory influence on striatal DA release and that the 5-HT4, but not the 5-HT1, 5-HT2 or 5-HT3, receptor subtyp e is implicated, at least partially, in this effect.