The GABAA agonist THIP (gaboxadol) increases non-REM sleep and enhances delta activity in the rat.
To investigate the effects of the selective gamma-aminobutyric acid (GABA)A receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol (THIP) on sleep, vehicle or 2 or 4 mg kg-1 of THIP were randomly administered i.p. to 8 rats at light onset. EEG and EMG were recorded during the first 6 hours after injection. THIP 4 mg kg-1 transiently evoked bursts of absence epilepsy-like EEG hypersynchronization. It significantly promoted non-rapid eye movement (non-REM) sleep and elevated delta activity within non-REM sleep. This was accompanied by an increase in both the rise rate and maximal level of delta activity within the non-REM sleep episodes. The effects of THIP on sleep resemble those reported earlier for the GABAA agonist muscimol and are dissimilar from those induced by benzodiazepine-agonistic modulators of GABAA receptors. These data indicate that agonists and agonistic modulators of GABAA receptors affect sleep differentially.
Lancel
M
M
Max-Planck Institute of Psychiatry, Department of Neuroendocrinology, Munich, Germany.
Faulhaber
J
J
D000818:Animals; D003700:Delta Rhythm / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012894:Sleep Stages / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles; C015542:gaboxadol