AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test

Todd D. Gould, Haim Einat, Ratan Bhat, Husseini K. Manji

Research output: Contribution to journalArticlepeer-review

289 Scopus citations

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 languageEnglish
Pages (from-to)387-390
Number of pages4
JournalInternational Journal of Neuropsychopharmacology
Volume7
Issue number4
DOIs
StatePublished - 1 Jan 2004
Externally publishedYes

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)

Fingerprint

Dive into the research topics of 'AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test'. Together they form a unique fingerprint.

Cite this