Effect of Treatment and Withdrawal from Chronic Lithium in Rats on Stimulant-Induced Responses

Lerer, Bernard; Globus, Mordecai Y.‐T.; Brik, E.; Hamburger, R.; Belmaker, Robert H.

doi:10.1159/000118046

Cited by 31 publications

(11 citation statements)

References 14 publications

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“…The effect of chronic lithium does not appear in all behavioral measurements of activity. As previously reported, lithium itself reduces activity in some (Lerer et al, 1984), but not all (Mattia et al, 1986) experiments. Forskolin powerfully and consistently reduces activity when given ip or icy (Wachtel et al, 1987;Barraco et al, 1985).…”

Section: Discussionsupporting

confidence: 84%

The effect of acute and chronic lithium on forskolin-induced reduction of rat activity

Bersudsky

Patishi

Jensen

et al. 1997

J. Neural Transmission

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Forskolin is a diterpene derivative that activates adenylate cyclase and raises cAMP levels in the cell. Both i.p. and i.c.v. forskolin cause behavioral hypoactivity. Lithium has been reported for many years to block cAMP accumulation, but the behavioral relevance of this biochemical effect is not clear. We studied the effect of acute and chronic lithium on icv forskolin-induced hypoactivity. Acute lithium had no effect, but chronic lithium significantly blocked forskolin-induced hypoactivity. The effect of chronic lithium occurred with both forskolin in DMSO and with a water-soluble forskolin derivative. These results suggest that this behavioral model can be used to investigate whether new inhibitors of adenylate cyclase possess lithium-like effects.

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Section: Discussionsupporting

confidence: 84%

The effect of acute and chronic lithium on forskolin-induced reduction of rat activity

Bersudsky

Patishi

Jensen

et al. 1997

J. Neural Transmission

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“…Thus, mice were tested in amphetamineinduced hyperlocomotor activity. Lithium at clinically relevant doses confirmed its effects in this model, in line with previous studies (Cox et al 1971;Lerer et al 1984). On the other hand, the GSK3 inhibitors AZ1080 and compound A were not effective, although compound A induced a decrease of mouse spontaneous activity.…”

Section: Discussionsupporting

confidence: 91%

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Caberlotto

Carboni

Zanderigo

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine kinase associated to neurological and psychiatric disorders. GSK3 inhibition is considered a mediator of the efficacy of the mood-stabiliser lithium. This study aimed at comparing the central nervous system effect of lithium with the selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and behavioural tests. Collapsin response mediator protein 2 is a neuron-specific GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in rat primary neurons with different pIC50. After systemic treatments with lithium or GSK3 inhibitors to assess specific functional responses, phosphorylation was unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors in pups, differently from lithium. Lithium may exert neurotrophic effect by increasing brain-derived neurotrophic factor (BDNF) levels: in the present experimental conditions, lithium exerted opposite effects on plasma BDNF levels compared to GSK3 inhibitors, suggesting this effect might not be necessarily mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and luteinising hormone were not affected by lithium, they were decreased by selective inhibitors. GH and prolactin displayed similar responses towards reduction. Follicle-stimulating hormone levels were not altered by treatments, whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 had no effects on locomotion, while compound A reduced spontaneous locomotor activity without effects on amphetamine-induced hyper-locomotion. The present results indicate that a broad correlation between the effects of lithium and selective GSK3 inhibitors could not be devised, suggesting alternative mechanisms, whereas overlapping results could be obtained in specific assays.

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“…Therefore it is difficult to evaluate these acute effects reported by Caron's group (Beaulieu et al 2004), especially in the light of the long history of contradictory results in this field. Several reports demonstrate inhibition of amphetamine-induced hyperactivity by acute and chronic lithium pretreatment in rats and mice (Berggren 1985;Berggren et al 1981Berggren et al , 1978Borison et al 1978;Flemenbaum 1974;Gould et al 2001;Hamburger-Bar et al 1986;Lerer et al 1984). However, other publications show absence of lithium effect in this model (Arriaga et al 1988;Cappeliez and Moore 1990;Ebstein et al 1980;Fessler et al 1982;Pittman et al 1984).…”

Section: Psychostimulants-induced Hyperactivitymentioning

confidence: 96%

Establishment of a Battery of Simple Models for Facets of Bipolar Disorder: A Practical Approach to Achieve Increased Validity, Better Screening and Possible Insights into Endophenotypes of Disease

Einat

2006

Behav Genet

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The lack of appropriate animal models for bipolar disorder (BPD) hinders the translation of novel molecular and genetic findings into the development of new more efficient treatments. Attempts to develop a comprehensive model for BPD did not result in a practical and valid model and at present most studies utilize a limited number of models for specific components of the disorder. Whereas there is a higher availability of models for the depression pole of BPD, only a few models represent the manic pole with the most frequently used being psychostimulant-induced hyperactivity. This last model had been important in studies of the disease and has some validity but it is clear that by itself cannot be considered to represent mania. Additional models for facets of BPD are needed to allow better screening of new drugs and new mutant mice. Such models may also support the exploration of endophenotypes of BPD and the mechanisms of the disease. An advantage of a battery approach is that each model can be only partially valid when used alone but the combination of a few models may result in strong validity. The present study suggests that such a battery can be based on existing models previously developed in the context of studying normal behavior or other disorders after an initial validation in the context of BPD. An example for this idea is described using the resident-intruder test for aggression. Present results show that 3 weeks oral treatment with 1.2-2.4% lithium (increasing doses), or 20 g/kg daily dose of valproate, significantly reduced aggressive behavior in resident mice without affecting non-aggressive social interactions. Accordingly, it is suggested that the simplified resident-intruder paradigm may model the aggression related to mania as part of a test battery for facets of BPD. It is further speculated that, pending further research, this paradigm can be combined with additional methods to explore changes in the LHPA axis that may be linked to an important endophenotype of BPD.

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Effect of Treatment and Withdrawal from Chronic Lithium in Rats on Stimulant-Induced Responses

Cited by 31 publications

References 14 publications

The effect of acute and chronic lithium on forskolin-induced reduction of rat activity

The effect of acute and chronic lithium on forskolin-induced reduction of rat activity

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Establishment of a Battery of Simple Models for Facets of Bipolar Disorder: A Practical Approach to Achieve Increased Validity, Better Screening and Possible Insights into Endophenotypes of Disease

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