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

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) and basal and fenfluramine‐induced 5‐HT release in the striatum. Separate groups of rats were treated with either vehicle or 5,7‐DHT (100μ 76% striatal 5‐HT depletion; or 200μ 93% styriatal 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 dosedependently reduced by 5,7‐DHT. In contrast, the increase of 5‐HT release produced by fenfluramine treatement (10 mg/kg) wa 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 th 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. © 1995 Wiley‐Liss, Inc.