MSI-1436 reduces acute food intake without affecting dopamine transporter activity

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 (C) 2010 Elsevier Inc All rights reserved