title: A simple and rapid method of inducing physical dependence with benzodiazepines in mice.
abstract: Physical dependence was rapidly induced in mice by administering diazepam intraperitoneally twice daily using an incremental dosing regimen (50 to 450 mg/kg) for nine consecutive days. Withdrawal was induced (24 hr after the last dose) by administration of a benzodiazepine antagonist, RO-15-1788 (10 mg/kg, IP). All of the mice exhibited clear-cut withdrawal symptoms (i.e., convulsions) within minutes of antagonist treatment. This method offers a simple, reliable, high throughput procedure for the assessment of benzodiazepine-like physical dependence liability and withdrawal, and it would be useful for screening purposes.
mesh_terms: D000818:Animals; D001569:Benzodiazepines; D003975:Diazepam / Q000008:administration & dosage; D005442:Flumazenil / Q000008:administration & dosage / Q000009:adverse effects; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced; D019966:Substance-Related Disorders
chemical_list: D001569:Benzodiazepines; D005442:Flumazenil; D003975:Diazepam