Psychiatry Research, 5, 67-76 (I 98 1) Elsevier/North-Holland Biomedical Press 67 Sleep Deprivation: Effects on Circadian Rhythms of Rat Brain Neurotransmitter Receptors Anna Wirz-Justice, Irene Tobler, Marian S. Kafka, Dieter Naber, Paul J. Marangos, Alexander A. Borbbly, and Thomas A. Wehr Received February 5. 1981; revised version receii*ed April 24, 1981; accepted M ay 11, 1981. Abstract. Specific binding of ligands to rat forebrain CY- and P-adrenergic, musca- rinic cholinergic, opiate, benzodiazepine, and striatal dopamine receptors was measured at 4-hour intervals during the last I3 hours of a 24-hour sleep deprivation period, and during the first 1 I hours of the recovery sleep period. In non-sleep- deprived controls a 24-hour rhythm in binding was evident. The minor differences between the sleep deprivation group and the control group consisted mainly in a reduced amplitude of the 24-hour rhythm under the sleep deprivation schedule. The results indicate that neither the 24-hour forced locomotion nor the subsequent prominent sleep rebound is accompanied by marked changes in the number of neurotransmitter receptors and their circadian rhythms. Key Words. Sleep deprivation, neurotransmitter receptors, circadian rhythms. A single night’s total sleep deprivation has an immediate, short-lasting therapeutic effect in many endogenous depressive patients (for review see Rudolf et al., 1977). The physiological and biochemical mechanisms underlying sleep deprivation therapy are unknown. It has been proposed that the antidepressant effect results from the modifi- cation of circadian rhythms (Pflug and Tiille, 1971; Papousek, 1975). We have developed a more explicit circadian model for affective illness and its treatment: Clinical evidence suggests that the phase-position of circadian rhythms in depression is abnormally advanced, and experimental evidence suggests that chronic treatment with antidepressant drugs delays the phase-position of circadian rhythms (Wehr et al., in press; Wehr and Goodwin, in press; Wehr and Wirz-Justice, in press). Antidepres- sant effects of drugs are relatively long-lasting; antidepressant effects of sleep depriva- tion are short-lived and usually abolished by recovery sleep. The present study was undertaken to compare the effect of drug treatment to that of a single night’s sleep deprivation on circadian rhythms. In rat brain we have demonstrated that many neurotransmitter systems (which have been the focus of studies of affective illness as well as the mode of action of antidepres- sant drugs) undergo circadian rhythms in the number of specific binding sites (Naber et al., 1980; Kafka et al., 1981; Naber et al., 1981; Kafka et al., 1981a, 19816; Anna Wirr-Justice. Ph.D., is at the Psychiatrische UniversitHtsklinik, Basel. Switzerland. Irene Tobler. Ph.D., and Alexander A. Borbely, M.D.. are at the Pharmakologisches Institut der Universitat Zurich, Zurich. Switzerland. Marian S. Kafka. Ph.D.. Dieter Naber, M.D., Paul J. Marangos, Ph.D.,andThomas A. Wehr. M.D.. are at the Intramural Research Program, National Institute of Mental Health, Bethesda. MD. (Reprint requests to Dr. Wirt-Justice. Pspchiatrische Universitiitsklinik. Wilhelm Klein Strasse 27. CH-4025 Baael, Switzerland.) 0165-1781/81/0000-0000/$02.50 @ Elsevier/North-Holland Biomediclil Press