Effect of repeated treatment with topiramate on the beta-endorphin plasma level in rats selectively bred for high and low alcohol preference.
Recent research indicates that topiramate has a role in the treatment of alcohol dependence. Topiramate has multiple mechanisms of action including enhancement of GABA-ergic inhibitory transmission and blocking excitatory glutamate neurotransmission, and modulating voltage-gated sodium and calcium ion channels and inhibiting carbonic anhydrase. In this study, we examined the effect of topiramate on endogenous opioid systems, which have an important role in the development of alcohol dependence. We investigated the beta-endorphin plasma level of animals with high- and low-risks of alcohol dependency after repeated treatment with topiramate. We used the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats, and treated them with topiramate at a dose of 80 mg/kg p.o. for 14 days. In WHP rats treatment with topiramate led to an increase in beta-endorphin plasma levels, which persisted at the same level even after a single injection of alcohol. The level of this peptide with topiramate was lower than in alcohol-injected WHP rats who did not receive topiramate. Beta-endorphin levels in WHP rats after topiramate or topiramate and ethanol treatment were similar to the basal level of this peptide in WLP rats. In WLP rats, topiramate did not prevent the ethanol-induced increase in beta-endorphin plasma level. We propose that administration of topiramate may have different effects on the opioid system involved in dependence according to genetic susceptibilities to alcoholism.
Zalewska-Kaszubska
Jadwiga
J
Department of Pharmacodynamics, Medical University of Lodz, Muszynskiego 1, PL 90-151 Lodz, Poland. jzalewska@pharm.am.lodz.pl
Gorska
Dorota
D
Dyr
Wanda
W
Czarnecka
Elzbieta
E
D000437:Alcoholism / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D000077236:Topiramate; D001615:beta-Endorphin / Q000097:blood*
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose; D001615:beta-Endorphin