CNS Drug Discovery & Therapy (Track)


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


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.