Midazolam, a short-acting benzodiazepine, resets the circadian clock of the hamster.
Treatment with the short-acting benzodiazepine, triazolam, has been found to induce changes in both behavioral and endocrine circadian rhythms in hamsters. The objective of this study was to determine if these effects of triazolam could be generalized to other short-acting benzodiazepines. Therefore, the effects of midazolam on the biological clock of the hamster were examined in detail. A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light. Midazolam injections produced maximal phase advances at circadian time (CT) 6 and 9 and maximal phase delays at CT 15 and 21. Doses of 2.5 mg or larger produced phase shifts that were significantly different from those produced by the vehicle controls. In addition, the phase-shifting effects of midazolam were completely blocked by administration of the benzodiazepine receptor antagonist, RO 15-1788, indicating that the phase-shifting actions of midazolam are mediated via benzodiazepine receptors. These results indicate that the previously reported effects of triazolam on the circadian clock can be generalized to other short-acting benzodiazepines.
Wee
B E
BE
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Turek
F W
FW
D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008874:Midazolam / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D013997:Time Factors
D005442:Flumazenil; D008874:Midazolam