Substituted Piperazine and Indole Compounds Increase Extracellular Serotonin in Rat Diencephalon As Determined by in Vivo Microdialysis

In vivo microdialysis was used to examine the effects of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU24969) and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) on extracellular 5-hydroxytryptamine (5-HT) in the diencephalon of unanesthetized rats. Both RU24969 and TFMPP are potent 5-HT autoreceptor agonists but both compounds caused a dose-dependent increase in extracellular 5-HT, when infused into the diencephalon at micromolar concentrations. The piperazine compound, TFMPP, also caused an increase in 5-HT when administered peripherally (2.5-10 mg/kg i.p.). In contrast, peripheral administration of RU24969 (2.5 mg/kg i.p.) caused a decrease in extracellular 5-HT. Since the effects of local infusion with RU24969 and TFMPP were not additive with the increase produced by the inhibitor of the uptake of 5-HT, fluoxetine, these compounds may be acting at the site of the membrane carrier. These results suggest that direct 5-HT1 agonist activity is not the only factor involved in the physiological and behavioral consequences of peripheral administration of TFMPP.