Abstract
The mechanism by which lithium exerts either its anti-manic or antidepressant effects remains to be fully elucidated. Although lithium inhibits the enzyme glycogen synthase kinase-3 (GSK-3) at concentrations that are relevant for treatment of bipolar disorder, it is unclear whether GSK-3-related mechanisms are responsible for its therapeutic effects in the treatment of this disease. We report that AR-A014418 (a selective GSK-3 inhibitor) induces behavioural changes that are consistent with the effects of antidepressant medications. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, a well-established model for antidepressant efficacy. In addition, the specificity of this effect is supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity. Taken together, these data support the hypothesis that lithium may exert its antidepressant effects through inhibition of GSK-3, and that novel small-molecule GSK-3 inhibitors may be useful for the treatment of bipolar disorder and depression.
Original language | English |
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Pages (from-to) | 387-390 |
Number of pages | 4 |
Journal | International Journal of Neuropsychopharmacology |
Volume | 7 |
Issue number | 4 |
DOIs | |
State | Published - 1 Jan 2004 |
Externally published | Yes |
Keywords
- Behaviour
- Depression
- Forced swim test
- Glycogen synthase kinase-3
- Mania
- Manic-depressive illness
ASJC Scopus subject areas
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)