title: Effects of the 5-HT(1A) Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats.
abstract: The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.
authors.affiliation: Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
authors.forename: Ryuki
authors.initials: R
authors.lastname: Tsutsui
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamei
mesh_terms: D000324:Adrenocorticotropic Hormone; D000818:Animals; D004195:Disease Models, Animal; D004569:Electroencephalography; D005445:Flunitrazepam / Q000494:pharmacology / Q000627:therapeutic use; D018757:GABA Modulators / Q000494:pharmacology / Q000627:therapeutic use; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D054833:Isoindoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects*; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D054833:Isoindoles; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C055267:tandospirone; D012701:Serotonin; D005445:Flunitrazepam; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D000324:Adrenocorticotropic Hormone