Facilitation of dopamine release in vivo by serotonin agonists: studies with microdialysis

Abstract

Using microdialysis, changes in extraneuronal levels of dopamine (DA), and the metabolites of DA and serotonin (5-HT), were monitored concurrent with perfusion of 5-HT1 agonists into the anterior striata of anesthetized rats. Perfusion of 5-HT facilitated DA release in a dose dependent manner, and to a greater extent than any other agonist tested. Extraneuronal DA levels increased 34% with perfusion of 0.04 nmol 5-HT and 18-fold with perfusion of 4.0 nmol 5-HT. Perfusion with multiple doses of either 1-(m-chlorophenyl)piperazine (m-CPP) or trifluoromethylphenylpiperazine (TFMPP) also resulted in a dose-dependent facilitation of DA release with a 40% increase in extracellular DA produced by either 0.4 nmol m-CPP or 10.0 nmol TFMPP. A 50-fold increase in DA followed 40.0 nmol m-CPP, while 160 nmol TFMPP enhanced DA 11-fold. Local application of either 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole succinate (RU24969) or 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (2.0 nmol perfused over 20 min) increased extracellular DA by 300 and 40%, respectively. RU24969 (2.0 nmol) also facilitated DA release following systemic pretreatment with 8-OH-DPAT (100 micrograms/kg). Perfusion with fenfluramine to release endogenous 5-HT also increased extraneuronal DA in a dose-dependent manner, and this facilitation was prevented by pretreatment with the 5-HT reuptake inhibitor fluoxetine. The facilitation of DA release by 0.4 nmol 5-HT was reduced by pretreatment with the 5-HT1 antagonist pindolol (4.0 nmol). These results suggest that serotonergic innervation of the anterior striatum may exert a facilitatory influence on DA release.