Independence of sleep EEG responses to GABAergic hypnotics: biological implications L. Palagini a , I.G. Campbell b , X. Tan b , M. Guazzelli a , I. Feinberg b, c, * a Psychiatry Clinic, University of Pisa, Pisa, Italy b Department of Psychiatry, University of California, Davis, CA 95616, USA c Veterans Administration Northern California Health Care System, Martinez, CA 94553, USA Received 19 January 2000; received in revised form 5 April 2000; accepted 21 April 2000 Abstract GABAergic hypnotics are known to depress non-rapid eye movement delta and rapid eye movements and to stimulate non-rapid eye movement sigma (spindles) and beta EEG. This study addressed the question of whether the magnitudes of these eects are signi®cantly correlated. Data were from a study in 16 normal subjects whose sleep was recorded for ®ve nights under placebo and for three nights each under zolpidem (10 mg), triazolam (0.25 mg) and temazepam (30 mg). EEG was analyzed with both period± amplitude and power spectral (FFT) analysis. The magnitudes of the EEG and eye movement density responses were not sig- ni®cantly correlated for any of the three drugs. It is therefore unlikely that sleep responses to GABAergic drugs can be explained by the common cellular action (increased chloride conductance) of these drugs. We suggest that the sleep EEG responses are mani- festations of complex (but consistent) interactions of excitation and inhibition in large brain systems although certain aspects of these responses (e.g. the dierent time courses of delta vs sigma and eye movement responses) may re¯ect molecular adaptations. A separate observation in this study was the strong traitlike characteristics of the sleep variables studied. These variables were highly correlated across nights of baseline sleep; in addition, individual dierences in baseline sleep were signi®cantly retained on the third night of temazepam administration. # 2000 Elsevier Science Ltd. All rights reserved. Keywords: Sleep; EEG; Computer; GABAergic eects; Intercorrelations; Reliability 1. Introduction GABAergic hypnotics produce a characteristic set of changes in sleep electrophysiology. In the non-rapid eye movement (NREM) EEG, power spectral analysis demonstrates that benzodiazepines depress delta (0.3± 3 Hz) power and increase spindle (12±15 Hz) and beta (15±23 Hz) power (Johnson et al., 1976, 1979, 1983). Period amplitude (PA) and hybrid methods of computer analysis also detect these eects (Gaillard et al., 1973; Gaillard and Aubert, 1975; Feinberg et al., 1977; Fein- berg, 1989) and can, in addition, distinguish the degree to which the changes in spectral power are produced by changes in wave amplitude as opposed to wave inci- dence. PA analyses demonstrate that benzodiazepines suppress both the amplitude and incidence of NREM delta waves, but that the amplitude suppression is greater (Feinberg et al., 1977, 1979). In contrast, ben- zodiazepines do not alter the amplitude of sigma and beta waves; the stimulation of Fast-Fourier Transform (FFT) power in these bands is entirely produced by increased wave incidence (Feinberg et al., 1995b). In addition to these EEG eects, GABAergic hypnotics depress the incidence of rapid eye movements during REM sleep [eye movement density (EMD)]. The sleep EEG eects have been most extensively described for benzodiazepines but recently developed non-benzodia- zepine GABAergic hypnotics (cf. Trachsel et al., 1990; Brunner et al., 1991) produce similar changes. Barbitu- rates reduce NREM delta (Feinberg et al., 1969) and decrease EMD (Oswald et al., 1963; Baekeland, 1967; Feinberg et al., 1969). The robust electrophysiological sleep ``signature'' of GABAergic hypnotics raises the question of whether the sleep responses are independent or intercorrelated. A search of the literature revealed no previous study of 0022-3956/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0022-3956(00)00019-4 Journal of Psychiatric Research 34 (2000) 293±300 www.elsevier.com/locate/jpsychires * Corresponding author. Tel.: +1-916-752-8628; fax: +1-916-752- 5350. E-mail address: ifeinberg@ucdavis.edu (I. Feinberg).