Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats

Abstract

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...

Chronic Ethanol Intake Alters Circadian Period‐Responses to Brief Light Pulses in Rats

“…Thus, although several ethanol-sensitive neurotransmitter and receptor systems are known to play key roles in circadian pacemaker regulation (Rosenwasser, 2001), the hypothesis that alcohol intake affects the circadian pacemaker via its action on these neural systems remains largely untested. This surprising lack of evidence stands in marked contrast to the extensive available data indicating that the central circadian pacemaker is indeed sensitive to several other classes of mood-altering psychoactive drugs, including antidepressants (Wollnik, 1992;Klemfuss and Kripke, 1994;Duncan et al, 1998), benzodiazepines (Turek and Losee-Olson, 1986;Subramanian and Subbaraj, 1996), and putative depressogenic agents (Rosenwasser, 1996).…”

“…For example, alterations in free-running circadian period have been described during chronic administration of several different classes of antidepressants (Wollnik, 1992;Klemfuss and Kripke, 1994;Rosenwasser and Wirz-Justice, 1997;Duncan et al, 1998), the anxiolytic benzodiazepine, diazepam (Subramanian and Subbaraj, 1996), the putative depressogenic agent, clonidine (Rosenwasser, 1996), and ethanol (Dwyer and Rosenwasser, 1998;Rosenwasser et al, 2005). Surprisingly, both lengthening and shortening of free-running period have been observed, even for a given agent, and these effects appear to be modulated by a variety of factors, including both lighting conditions and individual differences in baseline period (Rosenwasser, 1996;Rosenwasser et al, 2005).…”

Evaluation of serotonin, noradrenaline and dopamine reuptake inhibitors on light-induced phase advances in hamster circadian activity rhythms

“…Collectively, the present and previous data indicate that fluoxetine generally inhibits the influence of light on circadian activity rhythms in hamsters and mice. In contrast, in rats-a species in which serotonergic input to the circadian system mimics the effects of light (Kohler et al 2000)-chronic fluoxetine administration did not affect circadian wheel-running activity rhythms in subjects housed under constant darkness (Wollnik 1992). Further, fluoxetine induced nonphotic phase shifts in a rat hypothalamic slice preparation during the day after preloading of tryptophan to offset the loss of serotonergic input from the raphe (Sprouse et al 2006).…”

Effect of lithium carbonate on activity level and circadian period in different strains of rats

“…This notion is strengthened by several studies with antidepressant agents: clorgyline, for example, dampens activity and lengthens circadian period (5), whereas both moclobemide and desipramine increase activity and shorten period length (50). Further evidence derives from studies of the phase-shifting effect of pharmacological agents on the free-running rhythms, in which activity restriction after pharmacological application abolished chronobiological effects (43).…”