Akt/GSK3 signaling in the action of psychotropic drugs

Annu Rev Pharmacol Toxicol. 2009:49:327-47. doi: 10.1146/annurev.pharmtox.011008.145634.


Psychotropic drugs acting on monoamine neurotransmission are major pharmacological treatments for neuropsychiatric conditions such as schizophrenia, depression, bipolar disorder, Tourette syndrome, ADHD, and Alzheimer disease. Independent lines of research involving biochemical and behavioral approaches in normal and/or genetically modified mice provide converging evidence for an involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by dopamine and serotonin (5-HT). These signaling molecules have also received attention for their role in the actions of psychoactive drugs such as antidepressants, antipsychotics, lithium, and other mood stabilizers. Furthermore, investigations of the mechanism by which D2 dopamine receptors regulate Akt/GSK3 signaling strongly support the physiological relevance of a new modality of G protein-coupled receptor (GPCR) signaling involving the multifunctional scaffolding protein beta-arrestin 2. Elucidation of the contribution of multiple signaling pathways to the action of psychotropic drugs may provide a better biological understanding of psychiatric disorders and lead to more efficient therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Glycogen Synthase Kinase 3 / metabolism*
  • Humans
  • Lithium Compounds / metabolism
  • Lithium Compounds / pharmacology
  • Lithium Compounds / therapeutic use
  • Mental Disorders / drug therapy
  • Mental Disorders / physiopathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Psychotropic Drugs / metabolism
  • Psychotropic Drugs / pharmacology*
  • Psychotropic Drugs / therapeutic use
  • Signal Transduction*
  • Terminology as Topic


  • Antipsychotic Agents
  • Lithium Compounds
  • Psychotropic Drugs
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3