The noradrenaline reuptake inhibitor atomoxetine phase-shifts the circadian clock in mice

O'Keeffe, Saileog; Thome, Johannes; Coogan, Andrew N.

doi:10.1016/j.neuroscience.2011.11.002

Cited by 39 publications

(32 citation statements)

References 74 publications

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“…Acute doses of atomoxetine alter responses to phase shifting by light, as well as light-induced expression of a number of clock genes and immediate early genes in the SCN (O'Keeffe et al, 2012). Acute atomoxetine alters clock gene and immediate early gene expression in the SCN at phases when atomoxetine alone produces phase shifts, suggesting that it not only alters light input, but also the underlying transcription-translation feedback loops that give rise to the intracellular circadian clock.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that the results observed in those studies, as well as in the current study, may be due to an interaction between the circadian clock in the SCN and the MASCO. Recently, atomoxetine, another drug used in the treatment of ADHD that shows greater selectivity for the noradrenergic system, was shown to phase shift the circadian clock when given as a single dose (O'Keeffe et al, 2012). The direction of phase shift observed depended on lighting condition, in that administration during the mid subjective day caused large delays in constant light and small advances in constant dark.…”

Section: Discussionmentioning

confidence: 99%

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Methylphenidate Modifies the Motion of the Circadian Clock

Antle

Diepen

Deboer

et al. 2012

Neuropsychopharmacol

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People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Methylphenidate Modifies the Motion of the Circadian Clock

Antle

Diepen

Deboer

et al. 2012

Neuropsychopharmacol

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“…This animal is hyperactive, has deficits in nesting behaviors, and shows the same paradoxically lower levels of locomotor activity in response to amphetamines as shown by ADHD patients. Another therapeutic agent for ADHD, atomoxetine, has phase-dependent effects on the central SCN clock and amplifies the phase response to light in mice [68].…”

Section: Attention Deficit Hyperactivity Disorder (Adhd)mentioning

confidence: 99%

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf

McCarthy

Welsh

2014

Curr Psychiatry Rep

149

100

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Many psychiatric disorders are characterized by circadian rhythm abnormalities including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to, and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders including posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

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“…Recently, rodent studies have assisted in uncovering the potential molecular mechanisms behind the effects of ADs on chronobiology (Cuesta et al 2008;O'Keeffe et al 2011). Such studies may assist in explaining both the beneficial and sometimes detrimental effects of ADs on sleep and circadian rhythms.…”

Section: Antidepressantsmentioning

confidence: 99%

“…Such studies may assist in explaining both the beneficial and sometimes detrimental effects of ADs on sleep and circadian rhythms. A recent rodent study by O'Keeffe et al (2011) showed that atomoxetine, an NRI, can reset the circadian clock in a constant light exposure model (measured by c-Fos and ARC in the SCN). The beneficial effects of atomoxetine in inducing large phase delays in a constant light environment were mimicked by reboxetine.…”

Section: Antidepressantsmentioning

confidence: 99%

Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics

Eyre

Baune

2012

J Neural Transm

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The rising burden of unipolar depression along with its often related sleep disturbances, as well as increasing rates of sleep restriction in modern society, make the search for an extended understanding of the aetiology and pathophysiology of depression necessary. Accumulating evidence suggests an important role for the immune system in mediating disrupted neurobiological and chronobiological processes in depression. This review aims to provide an overview of the neuroimmunomodulatory processes involved with depression and antidepressant treatments with a special focus on chronobiology, chronotherapeutics and the emerging field of immune-circadian bi-directional crosstalk. Increasing evidence suggests that chronobiological disruption can mediate immune changes in depression, and likewise, immune processes can mediate chronobiological disruption. This may suggest a bi-directional relationship in immune-circadian crosstalk. Furthermore, given the immunomodulatory effects of antidepressants and chronotherapeutics, as well as their associated beneficial effects on circadian disturbance, we--and others--suggest that these therapeutic agents may exert their chronobiotic effects partially via the neuroimmune system. Further research is required to better elucidate the mechanisms of immune involvement in the chronobiology of depression.

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The noradrenaline reuptake inhibitor atomoxetine phase-shifts the circadian clock in mice

Cited by 39 publications

References 74 publications

Methylphenidate Modifies the Motion of the Circadian Clock

Methylphenidate Modifies the Motion of the Circadian Clock

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Neuroimmunomodulation in unipolar depression: a focus on chronobiology and chronotherapeutics

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