Effect of SX-3228, a selective ligand for the BZ(1) receptor, on sleep andwaking during the light-dark cycle in the rat

The effects of the benzodiazepine(1) (BZ(1)) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administra tion of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning s of the light phase of the light-dark cycle induced a significant reductio n of rapid-eye-movement sleep (REMS) during the third recording hour. Moreo ver, slow wave sleep (SWS) was increased during the fourth recording hour a fter the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the li ght-dark cycle caused a significant and maintained (6-h recording period) r eduction of waking (W), whereas SWS and light sleep (LS) were increased. RE MS values tended to increase during the entire recording period; however, t he increase was statistically significant only for the 1.0 mg/kg dose durin g the first recording hour. In addition, a significant and dose-related inc rease of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX- 3228 is a potent hypnotic when given to the rat during the dark period of t he light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat.