The GABAA agonist THIP (gaboxadol) increases non-REM sleep and enhances delta activity in the rat

Abstract

To investigate the effects of the selective γ-aminobutyric acid (GABA)A receptor agonist 4,5,6,7-tetrahydroisoxa-zolo(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 hyper-synchronization. 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.