The GABA(A) 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 br 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 GABA(A) agonist muscimol and are dissimilar from those induced by benzodiazepine-agonistic modulators of GABA(A) receptors. These data indicate that agonists and agonistic modulators of GABA(A) receptors affect sleep differentially.