Benzodiazepine dependence in mice after ingestion of drug-containing food pellets.
Diazepam was administered to Swiss-Webster mice for 53 days as a mixture of drug in laboratory chow, leading to consumption as high as 1000 mg/kg/day. Low plasma concentrations of diazepam, but very high levels (generally between 5,000 and 10,000 ng/ml) of the active metabolites nordiazepam and oxazepam, were found. Animals appeared healthy throughout drug administration, but some died because of apparent drug-induced aggression. Withdrawal was precipitated by omitting drug from the food. The behavior and physiological state of each animal were observed in detail during treatment and withdrawal phases. Tests that showed stable results in control animals and changes during abstinence were used to measure the withdrawal syndrome. These changes included piloerection, tremor, pelvic elevation and tail elevation, as well as changes in body tone, abdominal tone and pupil size. A composite withdrawal score was plotted against time; this score increased significantly (P less than .01) 1 day after withdrawal and remained significantly elevated for 17 days. This technique provides a quantitative method to study the effect of withdrawal from benzodiazepines in mice.
Gallaher
E J
EJ
Henauer
S A
SA
Jacques
C J
CJ
Hollister
L E
LE
D000374:Aggression / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents; D001835:Body Weight / Q000187:drug effects; D003975:Diazepam / Q000009:adverse effects / Q000097:blood; D004435:Eating / Q000187:drug effects; D008297:Male; D051379:Mice; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders
D014151:Anti-Anxiety Agents; D003975:Diazepam