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

Hafen, Thomas; Wollnik, Franziska

doi:10.1016/0091-3057(94)90252-6

Cited by 32 publications

(12 citation statements)

References 44 publications

(57 reference statements)

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“…Interestingly, both of these drugs have been repeatedly shown to alter the circadian period, leading to a long period in Drosophila, non-human primates, rodents and humans (Johnsson et al, 1983;Welsh and Moore-Ede, 1990;Klemfuss, 1992;Hafen and Wollnik, 1994;Dokucu et al, 2005). This effect on circadian rhythms likely involves the inhibition of GSK3β which modifies multiple members of the molecular clock (Iwahana et al, 2004;Padiath et al, 2004;Gould and Manji, 2005;Iitaka et al, 2005;Yin et al, 2006).…”

Section: Pharmacological Treatmentsmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

572

386

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For many years, researchers have suggested that abnormalities in circadian rhythms may underlie the development of mood disorders such as bipolar disorder, major depression and seasonal affective disorder. Furthermore, some of the treatments that are currently employed to treat mood disorders are thought to act by shifting or "resetting" the circadian clock, including total sleep deprivation and bright light therapy. There is also reason to suspect that many of the mood stabilizers and antidepressants used to treat these disorders may derive at least some of their therapeutic efficacy by affecting the circadian clock. Recent genetic, molecular and behavioral studies implicate individual genes that make up the clock in mood regulation. As well, important functions of these genes in brain regions and neurotransmitter systems associated with mood regulation is becoming apparent. In this review, the evidence linking circadian rhythms and mood disorders, and what is known about the underlying biology of this association, is presented.

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Section: Pharmacological Treatmentsmentioning

confidence: 99%

Circadian genes, rhythms and the biology of mood disorders

McClung

2007

Pharmacology & Therapeutics

572

386

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“…[145][146][147] Circadian rhythm disturbances may be a factor in bipolar disorder, and recent findings continue to support earlier reports that the circadian period can be altered by lithium. 148 This limited number of recent studies clearly indicates the need for further investigations of the hormonal and circadian influences of lithium.…”

Section: Physiological Effectsmentioning

confidence: 99%

Anti-bipolar therapy: mechanism of action of lithium

1999

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This review introduces the concepts that multiple actions of lithium are critical for its therapeutic effect, and that these complex effects stabilize neuronal activities, support neural plasticity, and provide neuroprotection. Three interacting systems appear most critical. (i) Modulation of neurotransmitters by lithium likely readjusts balances between excitatory and inhibitory activities, and decreased glutamatergic activity may contribute to neuroprotection.(ii) Lithium modulates signals impacting on the cytoskeleton, a dynamic system contributing to neural plasticity, at multiple levels, including glycogen synthase kinase-3␤, cyclic AMPdependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood recovery and stabilization. (iii) Lithium adjusts signaling activities regulating second messengers, transcription factors, and gene expression. The outcome of these effects appears likely to result in limiting the magnitudes of fluctuations in activities, contributing to a stabilizing influence induced by lithium, and neuroprotective effects may be derived from its modulation of gene expression.Keywords: lithium; bipolar disorder; inositol; glutamate; cyclic AMP; AP-1 Recent research suggests that understanding how lithium works in the treatment of bipolar disorder requires a different way of thinking about drug action. The vast majority of drugs are designed, by evolution or synthesis, to interact with single proteins, such as a specific receptor or enzyme. However, it now seems likely that multiple sites affected by lithium contribute to its mood-stabilizing action. Thus, the therapeutic action of lithium in bipolar disorder appears not to result from an effect at a single target site, but rather as the culmination of an integrated re-orchestration of a complex concert of events which effectively adjusts neuronal activity at multiple levels. Numerous effects of lithium have been identified, and some of these may each provide a necessary, but individually insufficient, component of the therapeutic response. One of the current challenges is to distinguish those critical effects from the many known biochemical actions of lithium, many of which may have little discernible effect, contribute to side effects, or lead to toxicity. Another challenge is to integrate the multiple effects of lithium into a comprehensive picture of how neuronal function is modulated by lithium. In retrospect, considering the complexities of mood, it perhaps should not be surprising that mood stabilization by lithium is also a complex process involving multiple actions. It is also important to keep in mind that lithium has efficacy as an antimanic agent, as a prophylactic agent for mania and depression, as a relatively weak antidepressant, and as an augmenter of the effects of many antidepressants. These multiple therapeutic effects of lithium along with the complexities of mood disorders and the multiplicity of affected systems inherent in these illnesses suggest that it is unlikely that all these ...

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“…Lithium has generally been shown to lengthen these rhythms, delaying their onset when a light-dark cycle is in place, and lengthening their periods when the animal is in constant darkness (Kripke and Wyborney, 1980;Poirel and Larouche, 1989;Stewart et al, 1991b;Hafen and Wollnik, 1994;Nagayama, 1996;Iwahana et al, 2004). The drug also allows the animals to adapt to the artificial extension of the circadian period, which is induced by establishing a light-dark cycle of longer than twenty-four hours (McEachron et al, 1981).…”

Section: The Effect Of Lithium On Circadian Behaviors In Rodentsmentioning

confidence: 99%

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

O’Donnell

Gould

2007

Neuroscience & Biobehavioral Reviews

121

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For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium.

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

Cited by 32 publications

References 44 publications

Circadian genes, rhythms and the biology of mood disorders

Circadian genes, rhythms and the biology of mood disorders

Anti-bipolar therapy: mechanism of action of lithium

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

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