THE GABA(A) AGONIST THIP INCREASES NON-REM SLEEP AND ENHANCES NON-REMSLEEP-SPECIFIC DELTA-ACTIVITY IN THE RAT DURING THE DARK PERIOD

Peripheral administration of the selective gamma-aminobutyric acid (GA BA(A)) receptor agonists muscimol and 4,5,6,7-tetrahydroisoxazolo(5,4- c)pyridin-3-ol (THIP) to rats has recently been found to increase non rapid eye movement sleep (non-REMS) duration and to enhance delta acti vity (0.5-4.0 Hz) within non-REMS during the light period, i.e. the ci rcadian rest phase. In this vehicle-controlled study, we investigated the sleep response to two doses of THIP (2 and 4 mg/kg) administered i ntraperitoneally to eight rats at the beginning of the dark period. El ectroencephalogram and electromyogram recordings were made continuousl y during the first 6-hours postinjection. The 4-mg/kg THIP dose signif icantly increased the time in non-REMS, lengthened the non-REMS episod es, and elevated delta activity within non-REMS. Quantitatively simila r, but smaller effects were induced by 2 mg/kg THIP. Neither dose of T HIP affected the time in REMS. These effects are very similar to those evoked by THIP and muscimol during the light period. This indicates t hat GABA(A) agonists dose-dependently promote non-REMS, by increasing non-REMS maintenance, and increase the in tensity of non-REMS, and tha t these effects are independent of the light-dark and circadian cycle.