MSI-1436 reduces acute food intake without affecting dopamine transporter activity |
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Authors: | Mitchell F Roitman Seth Wescott Michael P McLane |
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Institution: | a Department of Psychology, University of Illinois, Chicago, MC#285; 1007 W Harrison St. Chicago, IL 60607, USA b Department of Pharmacology, Genaera Corporation, 5110 Campus Dr. Plymouth Meeting, PA 19462, USA |
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Abstract: | Many therapies designed to reduce food intake and body weight act, in part, by blocking the dopamine transporter (DAT) — a protein responsible for clearing extracellular dopamine (DA) after release thereby terminating its action. Here, we found that a single injection of the drug trodusquemine (MSI-1436) decreased food intake in rats. To assess the effects of MSI-1436 on DAT function, fast-scan cyclic voltammetry was used to measure DA concentration changes in the ventral striatum. DA release was evoked by electrical stimulation of the ventral tegmental area every 5 min. After 3 baseline measurements, rats were injected with MSI-1436 (10 mg/kg), the known DAT blocker bupropion (80 mg/kg) or saline and evoked DA release and reuptake were monitored for an additional hour. Neither saline nor MSI-1436 caused a significant change in the magnitude of evoked release from baseline values whereas bupropion caused a significant increase. In addition, neither saline nor MSI-1436 significantly increased DA decay rates while such an increase was observed with bupropion. Thus, over a time course when MSI-1436 suppresses food intake it does not affect DAT function. The results support MSI-1436 as an anti-obesity treatment which spares DAT. |
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Keywords: | Obesity Striatum Voltammetry Motivation Reward |
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