Effect of destruction of serotonin neurons on basal and fenfluramine‐induced serotonin release in striatum

Abstract

This study examined the relationship between the magnitude of tissue serotonin (5-HT) depletion produced by treatment with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and basal and fenfluramine-induced 5-HT release in the striatum. Separate groups of rats were treated with either vehicle or 5,7-DHT (100 micrograms: 76% striatal 5-HT depletion; or 200 micrograms: 93% striatal 5-HT depletion). Four weeks after treatment, 5-HT release was measured in the ventral striatum using in vivo microdialysis in animals anesthetized with chloral hydrate. Basal 5-HT levels were not significantly altered in any lesion group, whereas basal 5-hydroxyindoleacetic acid levels were dose-dependently reduced by 5,7-DHT. In contrast, the increase of 5-HT release produced by fenfluramine treatment (10 mg/kg) was diminished significantly after 5-HT neuronal destruction in correlation with the reduction of striatal tissue 5-HT content. Fractional 5-HT efflux, a measure of the 5-HT release from surviving striatal nerve terminals, was also significantly elevated when tissue depletion of 5-HT exceeded 95%. This study suggests that compensatory mechanisms may enable surviving 5-HT terminals to maintain basal 5-HT levels in the striatum with as little as 5% of the terminals remaining, but those mechanisms are not sufficient to allow the damaged system to respond to a pharmacological challenge.