Evidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rat.

The present study, using the in vivo intracerebral microdialysis method, investigated the role of different serotonin receptor subtypes in the control of dopamine (DA) release exerted by serotonin (5-HT) in the striatum of halothane-anesthetized rats. Striatal dialysate DA content 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 demonstrate that under our experimental conditions, DA content reflects the neuronal origin of the neurotransmitter release. Drugs were locally applied by means of the microdialysis probe. One, 2.5 and 5 microM 5-HT significantly enhanced DA release in a concentration-dependent manner up to 157, 253 and 446% of basal values respectively. The effect induced by 1 microM 5-HT was not blocked by 10 microM (-)pindolol, a 5-HT1 receptor antagonist, 1 microM ketanserin or 10 microM cinanserin, both 5-HT2A antagonists. One or 10 microM ondansetron (GR 38032F), a selective 5-HT3 antagonist, were also ineffective. In contrast, 10 or 100 microM DAU 6285, a 5-HT3/4 antagonist, significantly reduced the effect of 5-HT on DA release (-20% and -60% respectively). Moreover, 100 microM BIMU 8, a selective 5-HT4 agonist, enhanced DA release (+85%) and this effect was reduced by 100 microM DAU 6285 (-40%). These results demonstrate that 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 subtype is implicated, at least partially, in this effect.