Physiolo¢,y& Behavior, Vol. 42, pp. 33-39. Copyright ~ Pergamon Journals Ltd., 1988. Printed in the U.S.A. 0031-9384/88 $3.00 + .00 Effects of Thyroidectomy, Parathyroidectomy and Lithium on Circadian Wheelrunning in Rats JONATHAN SCHULL,* DONALD L. McEACHRON,? NORMAN T. ADLER,+ LIZABETH FIEDLER,* JONATHAN HORVITZ,*ALISON NOYES,* MARTHA OLSON* AND JONATHAN SHACK* *Department of Psychology, Haverford College, Haverford, PA 19041 and tDepartment of Psychology, University of Pennsylvania, Philadelphia, PA 19104 Received 17 July 1986 SCHULL, J., D. L. McEACHRON, N. T. ADLER. L. FIEDLER, J. HORVITZ, A. NOYES, M. OLSON AND J. SHACK. Lf['ects of thyroidectomy, parathvroidectomy and lithium on circadian wheelrunning in rats. PHYS1OL BEHAV 42(I) 33-39, 1988.--Circadian rhythms and levels of wheelrunning were studied in thyroidectomized, parathyroidec- tomized, thyro-parathyroidectomized, and sham-operated male rats. Animals were entrained to a 12:12 light:dark schedule, then exposed to constant dim red illumination, and then given a diet containing lithium. Under constant condtions, free-running circadian activity rhythms were shorter, and levels of activitity were greater, in thyroidectomized and thyro- parathyroidectomized animals. Lithium reversed these effects, lengthening free-running circadian periods in all groups, with a greater reduction of activity observed in animals with thyroids removed. Parathyroidectomy had no clear effects. Since lithium slowed circadian rhythms and reduced activity even in the absence of intact thyroid or parathyroid glands, these effects may have been due to the action of lithium at some other site. The same may be true of other thyroid suppressors reported to affect circadian rhythms. These findings may be relevant to the biological substrates of major affective disorders in humans, which have been associated with abnormalities of thyroid function, abnormally short circadian rhythms, abnormal activity levels, and responsiveness to lithium therapy. Thyroidectomy Lithium Circadian rhythms Parathyroidectomy Wheelrunning Rats Activity Mania Depression Bipolar affective disorder IN an extended series of experiments involving removal of endocrine organs in animals, Richter [30] established that the 'master" circadian pacemaker does not reside in the endocrine system, and showed that a region near the anterior hypothalamus displayed pacemaker properties. That region has subsequently been identified as the suprachiasmatic nu- cleus [2]. Recent work indicates that endocrine and phar- macological manipulations do, however, influence circadian rhythms [2]. Circadian periods of behavioral activity in ro- dents, for example, are generally shortened by steroid hor- mones and lengthened by hypophysectomy [35]. Thyroid hormones also influence circadian rhythms. In rats exposed to 12:12 light:dark cycles, thyroidectomy at- tenuates or alters rhythms of feeding [4] and of plasma corti- costerone and prolactin [28]. In hamsters, free-running rhythms of locomotor activity were slowed by the thyroid inhibitors propylthiouracyl [26], and thiourea [3]. In canaries, behavioral activity rhythms were shortened by radiothyroidectomy [26] and lengthened by thyroxine [37]. Thyroid function and biological rhythms have also been linked in humans, since manic-depression and depression are associated with abnormalities of both rhythmicity and thyroid function [1, 8, 21]. The causal mechanisms involved are not clear [32,38], but it is known that symptoms of de- pression can be produced by hypothyroidism [41], hyper- thyroidism, and hyperparathyroidism [6,21]. Symptoms of mania and hyperactivity can be produced by hyper- thyroidism, and thyroid hormones can precipitate manic episodes in individuals with family histories of affective dis- ease [6,42]. With regard to biological rhythms, the disorders themselves involve seasonal [9, 34, 39], and circadian fluctua- tions in mood, and patients also display phase advances and fast free-running rhythms of temperature [16, 19, 29, 39], cor- ticosteroids [11,15], and rapid eye movement sleep (REM) [10,20]. The fact that several anti-depressant drugs lengthen circadian rhythms [40,44] also suggests that the association of fast circadian rhythms with affective disorders is not coincidental. Lithium, a major treatment for bipolar affective disorder, lengthens the free-running period of locomotion in rats [17] and of temperature and the sleep-wake cycle in humans [ 14], it also delays the phase of entrained activity rhythms in rats [25] and of the sleep/wake cycle in humans [18]. Lithium also suppresses the thyroid [7] and stimulates the parathyroid [13,23], raising the possibility that these glands play a role in the therapy as well as the etiology of circadian rhythm anomalies. The present experiments were designed to determine 33