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

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1 Brazilian Journal of Medical and Biological Research (1999) 3: Effect of SX-38 on sleep and waking ISSN 1-879X 17 Effect of SX-38, a selective ligand for the BZ 1 receptor, on sleep and waking during the light-dark cycle in the rat F. Alvariño 1, J.M. Monti 1, H. Jantos 1 and D. Monti 1 Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay Department of Psychiatry, University of Utah at Salt Lake City, Salt Lake City, UT, USA Correspondence J.M. Monti 833/6 Zudañez Street Montevideo 113 Uruguay Fax: jmonti@chasque.apc.org Received December 3, 1998 Accepted May 18, 1999 Abstract Key words SX-38 Benzodiazepine 1 receptor Sleep Waking REM sleep Zolpidem Light-dark cycle Introduction

2 18 F. Alvariño et al. a a Material and Methods

3 Effect of SX-38 on sleep and waking 19 Experiment 1 Experiment Procedures Data analysis Statistical analysis Results Experiments carried out during the light phase

4 11 F. Alvariño et al. 35 Wakefulness 1 Light sleep Control SX.5 SX 1. SX Slow wave sleep 1 1 REMS Figure 1 - The effect of SX-38 (SX) on wakefulness, light sleep, slow wave sleep and rapid-eye-movement sleep (REMS) during the light phase of the light-dark cycle. Ordinate: mean amount in minutes of behavioral state according to EEG criteria. All values are the means (min) ± SEM collected at 1-h intervals. Six animals were in each experimental group. Doses are reported in mg/kg. P<.5; P<.1 compared to control (Newman-Keuls test). Table 1 - Effect of SX-38 on sleep latencies during the light phase of the light-dark cycle. Data are reported as means ± SEM. Six animals were in each experimental group. The doses are reported as mg/kg. P<.5 compared to control (Newman-Keuls test). REMS, Rapid-eye-movement sleep. Slow wave sleep latency (min) REMS latency (min) Control 9.8 ± ± 17.7 SX ± ± ± ± ± ± 13.5 Experiments carried out during the dark phase

5 Effect of SX-38 on sleep and waking Wakefulness Control SX.5 SX 1. SX Light sleep 1 4 Slow wave sleep REMS Figure - The effect of SX-38 (SX) on sleep and waking during the dark phase of the light-dark cycle. All values are the means (min) ± SEM collected at 1-h intervals. Six animals were in each experimental group. Doses are reported in mg/kg. P<.5; P<.1 compared to control (Newman-Keuls test). REMS, Rapid-eye-movement sleep. Table - Effect of SX-38 on sleep latencies during the dark phase of the light-dark cycle. Values are reported as means ± SEM. Six animals were in each experimental group. The doses are reported as mg/kg. P<.5; P<.1 compared to control (Newman-Keuls test). REMS, Rapid-eyemovement sleep. Slow wave sleep latency (min) REMS latency (min) Control.6 ± ± 38.5 SX ± ± ±. 5.7 ± ± ±.6

6 11 F. Alvariño et al. EEG power density in nonrems (% of control) Discussion SX-38.5 mg/kg SX mg/kg SX-38.5 mg/kg Frequency (Hz) Figure 3 - Effect of SX-38 on the mean EEG power density of nonrems (non-rapid-eyemovement sleep) (relative to baseline) during the dark period of the light-dark cycle. The curves indicate mean values of successive frequencies which are reported as percent of the placebo reference value (= 1%) during a 6-h period. SX-38 significantly and dosedependently increased power density in the delta and theta regions ( P<.5; Newman- Keuls test).

7 Effect of SX-38 on sleep and waking 113 Acknowledgments

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Do non-benzodiazepine-hypnotics prove a valuable alternative to benzodiazepines for the treatment of insomnia?

Do non-benzodiazepine-hypnotics prove a valuable alternative to benzodiazepines for the treatment of insomnia? A. KNUISTINGH NEVEN, DEPARTMENT OF GENERAL PRACTICE, LEIDEN UNIVERSITY MEDICAL CENTER Introduction