A liquid diet model of chlordiazepoxide dependence in mice.
Mice fed chronically (3 to 4 weeks) a liquid diet containing chlordiazepoxide (CDP) became physically dependent on the drug as demonstrated by the occurrence of withdrawal signs precipitated by injection of the benzodiazepine antagonist Ro15-1788 (5 to 25 mg/kg) or by omitting CDP from the diet (spontaneous withdrawal). Very low blood concentrations of CDP, but medium to high levels of the active metabolites N-desmethyl CDP and demoxepam were found during the period of CDP administration. The Ro15-1788-induced withdrawal signs appeared within 1 min after the injection of the antagonist and lasted for at least 10 min. Quantifiable withdrawal signs included tail lift, tremor, impaired movement and handling-induced seizures. Mice undergoing spontaneous withdrawal had milder withdrawal signs such as weight loss, in appetite and suppression of runway and head-dipping activities on day 1 or day 2 of withdrawal. These signs were also present in Ro15-1788-induced withdrawal. A long-lasting rebound increase in runway and head-dipping activities occurred several days after CDP withdrawal.
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
M L
ML
D000818:Animals; D002707:Chlordiazepoxide / Q000008:administration & dosage* / Q000097:blood; D004032:Diet; D004195:Disease Models, Animal; D004326:Drinking; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders
D005442:Flumazenil; D002707:Chlordiazepoxide