Endogenous serotonin enhances the release of dopamine in the striatum only when nigro-striatal dopaminergic transmission is activated

In this study, we use in vivo microdialysis to investigate the influence of endogenous serotonin (5-HT) on striatal dopamine (DA) and 5-hydroxyidoleacetic acid (5-HIAA) efflux in both basal and activated conditions. The selective serotonin reuptake inhibitors citalopram and fluoxetine were used to mobilize endogenous 5-HT. In halothane-anaesthetized rats, citalopram (5 mg/kg, i.p.), administered either alone or in combination with the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg, s.c.), while reducing striatal 5-HIAA outflow (-25 and -15%, respectively), had no effect on basal DA output. When locally applied into the striatum, citalopram had no effect at 1 CIM concentration, but enhanced DA release after its perfusion at 25 and 100 mu M concentrations (+27% and +67%, respectively). However, the injection of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, failed to modify the effect of 25 mu M citalopram. In freely-moving rats, the intrastriatal infusion of citalopram or fluoxetine (1 mu M each), had no effect on its own, but significantly enhanced the increase in DA outflow induced by the subcutaneous administration of 0.01 mg/kg haloperidol (+31% and +30% for citalopram and fluoxetine, respectively). These findings indicate that, in the striatum, endogenous 5-HT has no influence on DA release under basal conditions, but positively modulates DA outflow when nigro-striatal DA transmission is activated. (C) 2000 Elsevier Science Ltd. All rights reserved.