The Interaction of Thyroid State, MAOI Drug Treatment, and Light on the Level and Circadian Pattern of Wheel-Running in Rats Wallace C. Duncan, Jr. and Jonathan Schull In order to examine the relationship between thyroid status, the circadian system, and antide- pressant drug response, the antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI), was administered chronically to sham-operated or thyroparathyroidectomized rats. Wheel-running was monitored continuously in a light-dark (LD) cycle, and then in constant dim light. In LD, MAOI treatment increased levels of running. This effect was delayed in hypothyroid rats relative to euthyroid rats. In constant light, the MAOl-induced increase in running was diminished in euthyroid but not hypothyroid animals. Hypothyroid animals were less responsive to the change in lighting than were euthyroid animals, and this was more apparent in hypothyroid rats given MAOI. The daily pattern of running differed with lighting condition as well as with treatment group. MAOI-treatment of hypothyroid animals phase-ad. vanced the pattern of wheel-running. MAOl-treatment of control animals increased the ampli- tude of wheel-running particularly in the LD cycle. These results indicate that thyroid status, lighting, and MAO! treatment interact to alter the behavioral response to chronic drug treatment. Key Words: Hypothyroidism, circadian rhythm, light, MAOI, depression, motor activity Introduction Altered thyroid function is frequently observed in patients with depressive illness (Bauer et al 1990; Cowdry et al 1983; Wehr et al 1988). The relationship between the two states is not clearly understood. Studies suggest that factors such as gender (Angst 1978; Goodwin and Jamison 1984), and history of treatment (Bauer et al 1990) are contributing factors (for review see Goodwin and Jamison 1990). Cate- cholamines and thyroid status may interact to influence the From the Clinical Psychobiology Branch, National Institutes of Mental Health, Beth. esda. MD (WCD); and The Department of Psychology, Havefford College, Havefford,PA (JS). Address reprint n~'queststo Wallace C. Duncan, Jr.. Rm 4S239, Bldg. 10, NIMH, Bethesda, IVlD 20892. Received May 11,1993; revised October 1,1993. course of affective illness as suggested by the observations that some depressed patients with mild thyroid abnormali- ties experience rapid cycling in mood during treatment with tricyclic antidepressants (Extein et al 1982; Wehr et al 1988). The antidepressant drug response seems to be modulated by the interaction of the thyroid and circadian systems. For example, the clinical effect of the tricyclic antidepressant imipramine (Whybrow and Prange 1981) and some monoa- mine oxidase inhibitors (MAOI) (Hullett and Bidder 1983; Joffe 1988) are potentiated by thyroid hormone, and in the case of tricyclic drugs, also by the thyrotoxin lithium (Za- jecka and Fawcett 1991). Nonpharmacological manipula- tions of the circadian system such as partial sleep depriva- tion (Leibenluft and Wehr 1992) or phase-advance of the 0 1994 Society of Biological Psychiatry 0006-3223/94/$07.00