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

✍ Scribed by Lynn G. Kirby; Deborah S. Kreiss; Ashish Singh; Irwin Lucki

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 731 KB
• Volume: 20
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/syn.890200202

✦ Synopsis

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 pg: 76% striatal5-HT depletion; or 200 pg: 93% striatal5-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 treatment (10 mgkg) 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 sdicient to allow the damaged system to respond to a pharmacological challenge. o 1995 Wiley-Liss, Inc.