WOLLNIK, F. E;ffects of chronic administration and Withdrawal of antidepressant agents on circadian activity rhythms in rats.PHARMACOL BIOCHEM BEHAV 43{2) S49-S61, 1992.-Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptalce inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotillne, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel-running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show proround abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period r was slightly shortened by moclobemide and dramatically shonened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters play a significant role in the neuronal control of behavioral state and circadian rhythmicity. Although the present study found that some antidepressives affect parameters of circadian rhythmicity, it could not demonstrate a common effect of all classes of antidepressives.
Circadian rhythmsGenetic differences Inbred strains Antidepressives Moclobemide Ro 19-6327 Desipramine Clomipramine Fluoxetine Levoprotiline IT has often been suggested that there is an association between the pathophysiology of affective disorders and disturbances of circadian rhythms. For example, studies in humans have shown that affective disorders are associated with abnormalities in the period, phase, and/or amplitude of physiological, behavioral, and endocrine rhythms, resulting in quite a number of different hypotheses on the chronobiology of depression (16,18,20,39,41). Special attention has been paid to the ob...