The effects of systemic administration and local microinjection into the central nervous system of the selective serotonin 5-HT2C receptor agonist RO-600175 on sleep and wakefulness in the rat.
The effects of RO-600175, a selective 5-HT2C receptor agonist, were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of RO-600175 (4 mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness and reduced slow wave sleep and rapid-eye-movement sleep during the first 2 h of the recording period. Direct infusion of RO-600175 into the dorsal raphe nucleus (4 mmol/l), laterodorsal tegmental nucleus (4 mmol/l), or horizontal limb of the diagonal band of Broca (4 mmol/l) also decreased rapid-eye-movement sleep. It is proposed that the activation of γ-aminobutyric acid-ergic cells located in the dorsal raphe nucleus, laterodorsal tegmental nucleus, and horizontal limb of the diagonal band of Broca is responsible, at least in part, for the effects of RO-600175 on rapid-eye-movement sleep. It is suggested that the increased wakefulness observed after systemic injection of the 5-HT2C receptor ligand could be partly related to the increased release of acetylcholine in the frontal cortex and hippocampus. However, additional studies are required to characterize the neurotransmitter systems responsible for the increase in wakefulness.
Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo, Uruguay.
Jaime M
JM
Monti
Héctor
H
Jantos
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000502:physiology; D004567:Electrodes, Implanted; D005021:Ethylamines / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D017440:Photoperiod; D017208:Rats, Wistar; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000008:administration & dosage*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D005021:Ethylamines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists