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The nature ofd,l-fenfluramine-induced 5-HT reuptake transporter loss in rats

  • Proceedings of the Symposium Cellular and Molecular Mechanisms of Drugs of Abuse Cocaine and Methamphetamine held in Nice, France, August 19–20, 1993
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Abstract

The administration of the anorexigenic drugd,l-fenfluramine (Ponderax®) to laboratory animals results in a dose-dependent reduction in presynaptically located serotonergic reuptake transporter protein. This long-term effect may represent an altered mechanism of synthesis of the transporter (downregulation). Alternatively, fenfluramine may destroy the serotonergic terminals on which 5-HT transporters are located. To distinguish between these two alternatives, we applied an assay of neurotransmitter-specific nerve endings (α) to brain tissue from two animal models of reduced 5-HT transporter density. In Model 1, serotonergic nerve terminals were destroyed (rats received 5,7-dihydroxytryptamine [5,7-DHT] intracisternally); in Model 2, there was a loss of 5-HT transportersper se on otherwise intact serotonergic nerve terminals. The manner in which α declined as transporter density was decreased (reducingV max values) in animal Models 1 and 2 was found to be significantly different. In rats treated with fenfluramine, the association between 5-HT transporter density and α was the same as in the neurotoxic model.

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  1. Clinical Research Centre, Royal Brisbane Hospital Foundation, Bancroft Centre, 4029, Brisbane, Q, Australia

    Robert Ian Westphalen & Peter Ronald Dodd

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  1. Robert Ian Westphalen
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Westphalen, R.I., Dodd, P.R. The nature ofd,l-fenfluramine-induced 5-HT reuptake transporter loss in rats. Mol Neurobiol 11, 165–175 (1995). https://doi.org/10.1007/BF02740693

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