Flumazenil (Ro15-1788) does not affect ethanol tolerance and dependence.
There are conflicting reports concerning whether flumazenil (Ro15-1788) can antagonize the central effects of ethanol and ethanol withdrawal reactions. C57BL/6J mice were treated chronically with an ethanol liquid diet. Control mice were pair fed an isocaloric diet containing no ethanol. These mice were injected with either Ro15-1788 (25 mg/kg) or vehicle immediately before, 14 h or 24 h before ethanol withdrawal. Under these conditions, no attenuation of the severity of handling-induced withdrawal seizures or of withdrawal hypothermia was observed in the ethanol-dependent mice injected with Ro15-1788. Likewise, there was no abolition or attenuation of tolerance to the ataxic effects (sleep time and horizontal dowel tests) and hypothermic effects of ethanol by Ro15-1788 when the mice were tested on day 3 of ethanol withdrawal. It is concluded that Ro15-1788 (25 mg/kg) has no effect on ethanol tolerance and dependence.
Chan
A W
AW
Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Leong
F W
FW
Schanley
D L
DL
Langan
M C
MC
Penetrante
F
F
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004032:Diet; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology*; D006234:Handling, Psychological; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012640:Seizures / Q000209:etiology; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*
D000431:Ethanol; D005442:Flumazenil