title: Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats.
abstract: The present study was performed to examine whether or not rebound insomnia is caused by an abrupt withdrawal of benzodiazepine hypnotics and tandospirone in rats. Etizolam and triazolam caused a significant shortening of sleep latency, increase in non-REM sleep time, and decrease in wake time in a dose-dependent manner. Etizolam and triazolam caused a significant shortening of sleep latency during drug administration (for 7 days), whereas a significant prolongation of sleep latency was observed by the abrupt withdrawal of these drugs. Tandospirone caused a shortening of sleep latency, whereas no effect was observed on non-REM sleep time and wake time during drug administration (for 7 days). On the other hand, tandospirone showed no significant effect on sleep latency through its abrupt withdrawal, differing from etizolam and triazolam. From these findings, a rebound phenomenon in terms of sleep latency was confirmed with etizolam and triazolam in rats. Furthermore, the 5-HT(1A) agonist, tandospirone, caused no rebound phenomenon regarding sleep latency in rats.
authors.affiliation: Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirase
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ishida
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: D000818:Animals; D003975:Diazepam / Q000008:administration & dosage / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D054833:Isoindoles / Q000008:administration & dosage; D008297:Male; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects*; D013997:Time Factors; D014229:Triazolam / Q000008:administration & dosage; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D006993:Hypnotics and Sedatives; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone; D014229:Triazolam; C044610:etizolam; D003975:Diazepam