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.
Roitman
Mitchell F
MF
Department of Psychology, University of Illinois, Chicago, IL 60607, USA. mroitman@uic.edu
Wescott
Seth
S
Cone
Jackson J
JJ
McLane
Michael P
MP
Wolfe
Henry R
HR
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D002776:Cholestanes / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
C441128:3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate; D019440:Anti-Obesity Agents; D002776:Cholestanes; D050483:Dopamine Plasma Membrane Transport Proteins; D013096:Spermine