CHRONIC ADMINISTRATION OF IMIPRAMINE AND LITHIUM CHANGES THE PHASE-ANGLE RELATIONSHIP BETWEEN THE ACTIVITY AND CORE BODY-TEMPERATURE CIRCADIAN-RHYTHMS IN RATS

Evidence suggests that there is an association between the pathophysio logy of depression and a disturbance of circadian rhythms. Accordingly , attention has focused on the possible effects of antidepressants on circadian rhythms. In the present study, we examined the effects of ch ronic administration of two clinically effective antidepressant agents , imipramine and lithium, on several circadian rhythms in the rat. Act ivity, core body temperature, and drinking rhythms were assessed in co nstant darkness (DD) and light-dark (LD) conditions. In DD, lithium si gnificantly lengthened the circadian period of the activity, temperatu re, and drinking rhythms, while imipramine had no effect. In LD, both drugs significantly delayed the phase of the activity rhythm, but did not change that of the other two rhythms. As a result, the phase-angle differences between the activity and temperature rhythms significantl y increased. Neither lithium nor imipramine produced any effect on the resynchronization of these rhythms after an 8-h delay in the LD cycle . These results indicate that although both drugs produced different e ffects on the circadian period of individual rhythms, both caused a re lative phase advance of the temperature rhythm as compared to the acti vity rhythm, and this effect may be related to the similarity in their antidepressant effects.