Youssef Sari

Adjunct Assistant Professor of Medicinal and Biological Chemistry, University of Toledo, College of Pharmacy & Pharmaceutical Sciences, Department of Pharmacology, Health Science Campus, Mail Stop 1015, 3000 Arlington Avenue, HEB283C, Toledo, OH  43614, USA

Abstract:

Ample evidence demonstrated the importance of glutamatergic system in alcohol dependence.  We have recently shown that upregulation of glutamate transporter 1 (GLT1) in central brain reward regions was associated in part with reduction in ethanol consumption in alcohol preferring (P) male rats.  GLT1 is a glial protein that regulates the majority of glutamate uptake in the brain.  In this study, we investigated the effects of a synthetic compound known as a GLT1 activator, MS-153, on ethanol drinking behavior in male P rats.  P rats were given 24-hour concurrent access to 15% and 30% ethanol, water and food for five weeks.  On week 6, P rats received MS-153 at doses 10, 20 or 50 mg/kg (i.p.) or a saline vehicle (i.p.) for five consecutive days.  We also have tested the effect of MS-153 (50 mg/kg, i.p.) on daily sucrose (10%) intake as a control for motivated drinking behavior.  Statistical analyses exhibited a significant decrease in ethanol consumption with the higher dose of MS-153 (50 mg/kg, i.p.) from Day 1 (24 hrs after the first i.p. injection) through Day 5 as compared to vehicle group.  In addition, we have observed a moderate effect with the lower doses (10 and 20 mg/kg, i.p.) starting Day 3 through Day 5.  Statistical analyses demonstrated a dose-dependent effect in ethanol intake.  However, we did not observe any significant effects of MS-153 with the three doses on the body weight.  Importantly, MS-153 at higher dose (50 mg/kg, i.p.) did not induce any effect on sucrose intake, which suggests the specific effect of MS-153 in ethanol intake.  These findings revealed MS-153 as a potential therapeutic compound for the treatment of alcohol dependence.