Interaction between the serotonergic, dopaminergic, and glutamatergic systems in fenfluramine-induced Fos expression in striatal neurons

✍ Scribed by M.J. Guerra; I. Liste; J.L. Labandeira-Garcia

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 633 KB
• Volume: 28
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199801)28:1<71::aid-syn9>3.0.co;2-9

✦ Synopsis

Fenfluramine (FE) is a halogenated amphetamine derivative used in the treatment of obesity and thought to induce serotonin (5-HT) release from nerve terminals and to reduce re-uptake. However, other pathways may also be involved. In this work, the effects of FE on the major striatal afferent systems, and the possible interactions of these systems in FE-induced striatal expression of Fos, were studied by lesion of the serotonergic and/or dopaminergic system and administration of NMDA glutamate (MK-801) or D 1 dopamine (SCH-23390) receptor antagonists. Both the D 1 and NMDA receptor antagonists suppressed Fos expression in response to FE almost entirely. FE-induced Fos expression was also dramatically reduced 24 h after 6-hydroxydopamine (6-OHDA) lesion of the dopaminergic system. However, the reduction was not so marked after chronic 6-OHDA lesion, probably due to compensatory changes. Chronic (5,7dihydroxytryptamine injection, 4 weeks before) or acute (p-chlorophenylalanine injection) lesion of the serotonergic system led to a marked reduction in Fos expression in response to FE (decrease of about 50%). After simultaneous chronic lesion of both serotonergic and dopaminergic systems, a considerable number of Fos-positive nuclei were still observed (decrease of about 70% in the dorsal and dorsomedial regions). The FE-induced expression of Fos was almost totally suppressed (decrease of about 95% in the dorsal and dorsomedial regions) after simultaneous acute lesion. Our results indicate that FE-induced striatal expression of Fos is due in large measure to DA release and dopaminergic stimulation of D 1 receptors. However, concurrent stimulation of NMDA glutamate receptors also appears to be essential, and 5-HT release (although not indispensable) doubles striatal Fos expression.