A novel action of lithium: Stimulation of glutamate release and inositol 1,4,5 trisphosphate accumulation via activation of the N-methyl D-aspartate receptor in monkey and mouse cerebral cortex slices

Hokin, Lowell E.; Dixon, John F.; Los, Georgyi V.

doi:10.1016/0065-2571(95)00021-6

Cited by 43 publications

(27 citation statements)

References 13 publications

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“…Biochemically diverse effects of lithium on the glutamateric system have been identified by a number of groups (Antonelli et al, 2000;Dixon and Hokin, 1998;Dixon et al, 1994;Du et al, 2004;Du et al, 2006;Gray et al, 2003;Hokin et al, 1996;Marcus et al, 1986). Specifically, these effects include evidence suggesting a decrease in glutamate reuptake, decrease in glutamate release, and/or modulation of receptor levels.…”

Section: Discussionmentioning

confidence: 99%

“…Among the many biochemical effects of lithium, evidence has suggested actions on the glutamateric system (Antonelli et al, 2000;Dixon and Hokin, 1998;Dixon et al, 1994;Du et al, 2004;Hokin et al, 1996;Marcus et al, 1986). A substantial body of data suggests that the AMPA receptor subclass of glutamate receptors may be particularly interesting targets for the treatment of mood disorders (Alt et al, 2006;Li et al, 2001;Li et al, 2003;Martinez-Turrillas et al, 2002; Svenningsson et al, 2002).…”

Section: Nih Public Accessmentioning

confidence: 99%

“…Lithium, in particular, has been implicated in modulating the glutamatergic system and AMPA receptors (Antonelli et al, 2000;Dixon and Hokin, 1998;Dixon et al, 1994;Du et al, 2004;Hokin et al, 1996;Marcus et al, 1986). Given the clinical profile of lithium, we hypothesized that regulation of AMPA receptor activation may be implicated in the antidepressant-like effects of lithium in the FST and TST.…”

Section: Experiments 4: Effects Of Ampa Receptor Blockade On the Antidmentioning

confidence: 99%

“…Thus, lithium has a clinical profile as an antidepressant medication, but understanding the therapeutic mechanism of lithium action has been a major challenge for psychiatric neuroscience, and lack of knowledge regarding how lithium exerts its therapeutic effects has likely hindered the development of novel antidepressant medications. To narrow the effects of lithium that are most likely related to the therapeutic actions of the drug, we have begun studying the neurobiology underlying the effects of lithium in established behavioral models.Among the many biochemical effects of lithium, evidence has suggested actions on the glutamateric system (Antonelli et al, 2000;Dixon and Hokin, 1998;Dixon et al, 1994;Du et al, 2004;Hokin et al, 1996;Marcus et al, 1986). A substantial body of data suggests that the AMPA receptor subclass of glutamate receptors may be particularly interesting targets for the treatment of mood disorders (Alt et al, 2006;Li et al, 2001;Li et al, 2003;Martinez-Turrillas et al, 2002; Svenningsson et al, 2002).…”

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Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

et al. 2008

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In addition to its clinical antimanic effects, lithium also has efficacy in the treatment of depression. However, the mechanism by which lithium exerts its antidepressant effects is unclear. Our objective was to further characterize the effects of peripheral and central administration of lithium in mouse models of antidepressant efficacy as well as to investigate the role of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in these behaviors. We utilized the mouse forced swim test (FST) and tail suspension test (TST), intracerebroventricular (ICV) lithium administration, AMPA receptor inhibitors, and BS3 crosslinking followed by western blot. Both short-and long-term administration of lithium resulted in robust antidepressant-like effects in the mouse FST and TST. Using ICV administration of lithium, we show that these effects are due to actions of lithium on the brain, rather than to peripheral effects of the drug. Both ICV and rodent chow (0.4% LiCl) administration paradigms resulted in brain lithium concentrations within the human therapeutic range. The effects of lithium to decrease immobility in the FST and TST were blocked by administration of AMPA receptor inhibitors. Additionally, administration of lithium increased the cell surface expression of GluR1 and GluR2 in the mouse hippocampus. Collectively, these data show that lithium exerts centrally mediated antidepressant-like effects in the mouse FST and TST that require AMPA receptor activation. Lithium may exert its antidepressant effects in humans through AMPA receptors, thus further supporting a role of targeting AMPA receptors as a therapeutic approach for the treatment of depression. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Depression is a severe neuropsychiatric disorder that manifests both as a component of bipolar disorder and unipolar depressive disorder. Bipolar disorder affects at least 1% of the world's population when a strict definition (DSM IV bipolar I disorder) is applied. Major depression is more common than bipolar disorder in the overall population (~ 15% lifetime risk as defined by DSM IV) (Kessler et al., 2005;Sullivan et al., 2000). The recognition of the significant morbidity and mortality (suicide rate of 15%) associated with these severe mood disorders (Evans et al., 2005;Jamison, 2000;Kupfer, 2005), as well as the growing appreciation that a significant percentage of patients either do not respond fully to existing treatments or are intolerant of undesirable side effects, has made the challenge of discovering improved therapeutic agents increasing...

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Section: Discussionmentioning

confidence: 99%

Section: Nih Public Accessmentioning

confidence: 99%

Section: Experiments 4: Effects Of Ampa Receptor Blockade On the Antidmentioning

confidence: 99%

mentioning

confidence: 99%

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Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

et al. 2008

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“…In recent years, it has been indicated that lithium may affect the biophysical properties of ionotropic glutamate receptors [6,7]. It was also established that lithium exerts its neuroprotective effect through the reduction of NMDA receptor-induced excitotoxicity [5,12]. This has been confirmed in animal models where radio-ligand binding of [3H]-MK801 or other NMDA receptor antagonists was decreased in the cerebral cortex of mice after the chronic administration of antidepressant drugs [8,14].…”

Section: Introductionmentioning

confidence: 90%

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

Szczepankiewicz

Skibińska

Suwalska

et al. 2009

Pharmacological Reports

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Abstract:We investigated three polymorphisms in the NMDA receptor 2B subunit gene (GRIN2B) as a candidate gene for lithium response involved in glutamatergic neurotransmission. One hundred five bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as excellent -no affective episodes during lithium treatment; partial -50% reduction in the episode index; or no response -less than 50% reduction, no change or worsening in the episode index. Genotypes for the -200G/T, 366C/G and rs890G/T GRIN2B polymorphisms were established using the PCR-RFLP method. Genotype distributions were in Hardy-Weinberg equilibrium for all three polymorphisms. No association was found between the three polymorphisms studied and the treatment response to lithium. The authors conclude that polymorphisms of the GRIN2B gene did not show an association with the treatment response to lithium in bipolar patients.

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Differential effects of acute and short-term lithium administration on dialysate glutamate and GABA levels in the frontal cortex of the conscious rat

Antonelli

Ferioli²,

Gallo³

et al. 2000

Synapse

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In the present study, we employed in vivo microdialysis in the frontal cortex of the awake rat to investigate the effects of acute and short‐term (twice daily, 3 days) lithium chloride administration (1, 2, and 4 meq/kg, s.c.) on local dialysate glutamate and GABA levels. Acute lithium (1 meq/kg) failed to influence cortical glutamate levels while the higher (2 and 4 meq/kg) doses increased (+38 ± 6% of basal levels) and reduced (‐27 ± 4%) cortical glutamate levels, respectively. Cortical GABA levels were affected by acute lithium only at the highest 4 meq/kg dose (+62 ± 6%). Furthermore, these effects were prevented by tetrodotoxin (1 μM) and low‐calcium (0.2 mM) medium perfusion. Following short‐term administration, lithium increased (+58 ± 4%) cortical dialysate glutamate levels at the 1 meq/kg dose, was ineffective at 2 meq/kg, while the effect of the 4 meq/kg dose was similar to that observed after acute administration. Interestingly, intracortical perfusion with the GABAB receptor antagonist CGP 35348 (100 μM) reversed the acute lithium (4 meq/kg)‐induced decrease in glutamate levels. Taken together, these findings indicate a differential dose and duration dependent effect of lithium on cortical dialysate glutamate levels involving both a direct enhancement and an indirect inhibition that is mediated via an activation of local GABAB receptor. These findings may be relevant for the therapeutic effects of the drug. Synapse 38:355–362, 2000. © 2000 Wiley‐Liss, Inc.

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A novel action of lithium: Stimulation of glutamate release and inositol 1,4,5 trisphosphate accumulation via activation of the N-methyl D-aspartate receptor in monkey and mouse cerebral cortex slices

Cited by 43 publications

References 13 publications

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

Differential effects of acute and short-term lithium administration on dialysate glutamate and GABA levels in the frontal cortex of the conscious rat

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