Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster mice.
Topiramate has emerged as one of the promising drugs for the treatment of alcoholism and alcohol addiction. Recent studies have shown that topiramate reduces harmful drinking and initiates abstinence in humans, but little is known as to why this drug is effective.


OBJECTIVE
In the present study, we examined the effects of topiramate in reducing convulsions during alcohol withdrawal using a procedure called the handling-induced convulsion (HIC) test in male Swiss-Webster mice. In addition, we examined the ability of topiramate to reduce alcohol conditioned and anxiety related behaviours during conditioned abstinence using the elevated plus maze (EPM) test.


METHODS
HICs were examined 10 h after the 3rd daily alcohol (2.5 g/kg; 20% w/v)+4 methylpyrazole (4MP) (9 mg/kg) intraperitoneal (i.p.) injection with topiramate (0, 10 or 20 mg/kg ip) administered 30 min before testing. In the EPM, alcohol (1.75 g/kg; 20%, i.p.) or saline was administered daily for 9 days and subjects were immediately placed on the maze. Anxiety related behaviours included the amount of time spent and number of entries in the open or closed arms and grooming bouts, and conditioned behaviours including the stretched-attend posture were examined 24 h after the last day of alcohol injection.


RESULTS
Topiramate (10 and 20 mg/kg) significantly reduced HIC scores (P<0.05) compared to the alcohol/saline group. In the EPM, topiramate (20 mg/kg) reduced the stretched-attend postures (P<0.001) compared to the alcohol/saline group.


CONCLUSIONS
These findings suggest that topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned behaviours during conditioned abstinence in Swiss-Webster mice.
Farook
Justin M
JM
Department of Psychology, Kastle Hall, University of Kentucky, Lexington, Kentucky 40506, USA. justinfarook@uky.edu
Morrell
Dennis J
DJ
Lewis
Ben
B
Littleton
John M
JM
Barron
Susan
S
D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000494:pharmacology*; D001007:Anxiety / Q000517:prevention & control / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006234:Handling, Psychological; D008297:Male; D051379:Mice; D011187:Posture; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000517:prevention & control* / Q000523:psychology; D000077236:Topiramate
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D000077236:Topiramate; D005632:Fructose; D000431:Ethanol