Topiramate reduces ethanol consumption by C57BL/6 mice.
BACKGROUND
Previous reports indicate that topiramate (TPM) might be an effective treatment for alcohol dependence, perhaps due to a decrease alcohol's rewarding effects resulting from inhibition mesocorticolimbic dopamine (DA) release. Additional reports indicate that TPM antagonizes chronic changes induced by alcohol at the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptors. In the present study, a C57BL/6 (B6) murine model (n = 40) was used to evaluate the effect of TPM on the consumption of 12% alcohol over a 21-h period.


METHODS
TPM (0, 10, 30, 90 mg/kg) injected subcutaneously into B6 mice 60 min prior to access to a 12% ethanol solution (v/v) over 8 days produced dose-responsive reduction in consumption during the first 2-h period after injection.


RESULTS
Across the 8 days of treatment ethanol intake (g/kg) for SAL, T10, T30, and T90, respectively, was 1.34, 1.03, 0.72, and 0.67. This reduction appears to require systemically available TPM since it was not statistically supported when assessed over the entire 21-h period of ethanol availability. None of the TPM doses affected food consumption or body weight, and T90 dose did not reduce motor activity either by itself or in combination with ethanol.


CONCLUSIONS
Unlike previous experiments using the same B6 mouse model to assess naltrexone or tiagabine, there was no evidence that mice developed tolerance to the TPM-induced reductions in ethanol consumption. Thus, in the B6 mouse, TPM reduced ethanol intake at doses with no readily apparent adverse side effects, an effect consistent with recent clinical reports. Additional study will be directed toward characterizing TPM as a treatment for alcohol dependence.
Nguyen
Shaun A
SA
Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina 29482, USA.
Malcolm
Robert
R
Middaugh
Lawrence D
LD
D000284:Administration, Oral; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D018091:Receptors, AMPA; D000077236:Topiramate; D005632:Fructose; D000431:Ethanol