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 (G ABA)(A) receptor agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-o l (THIP) on sleep, vehicle or 2 or 4 mg kg(-1) of THIP were randomly a dministered i.p. to 8 rats at light onset. EEG and EMG were recorded d uring the first 6 hours after injection. THIP 4 mg kg(-1) transiently evoked bursts of absence epilepsy-like EEG hypersynchronization. It si gnificantly promoted non-rapid eye movement (non-REM) sleep and elevat ed delta activity within non-REM sleep. This was accompanied br an inc rease in both the rise rate and maximal level of delta activity within the non-REM sleep episodes. The effects of THIP on sleep resemble tho se reported earlier for the GABA(A) agonist muscimol and are dissimila r 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.