Rebound insomnia induced by abrupt withdrawal of hypnotics in sleep-disturbed rats.
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.
Hirase
Masahiro
M
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Ishida
Takayuki
T
Kamei
Chiaki
C
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*
D006993:Hypnotics and Sedatives; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone; D014229:Triazolam; C044610:etizolam; D003975:Diazepam