Cellular Plasticity Cascades: Genes-To-Behavior Pathways in Animal Models of Bipolar Disorder

Haim Einat, Husseini K. Manji

Research output: Contribution to journalReview articlepeer-review

121 Scopus citations


Background: Despite extensive research, the molecular/cellular underpinnings of bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated that mood stabilizers exert major effects on signaling that regulate cellular plasticity; however, a direct extrapolation to mechanisms of disease demands proof that manipulation of candidate genes, proteins, or pathways result in relevant behavioral changes. Methods: We critique and evaluate the behavioral changes induced by manipulation of cellular plasticity cascades implicated in BD. Results: Not surprisingly, the behavioral data suggest that several important signaling molecules might play important roles in mediating facets of the complex symptomatology of BD. Notably, the protein kinase C and extracellular signal-regulated kinase cascades might play important roles in the antimanic effects of mood stabilizers, whereas glycogen synthase kinase (GSK)-3 might mediate facets of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR) modulation also seems to be capable to inducing affective-like changes observed in mood disorders. And Bcl-2, amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, and inositol homeostasis represent important pharmacological targets for mood stabilizers, but additional behavioral research is needed to more fully delineate their behavioral effects. Conclusions: Behavioral data support the notion that regulation of cellular plasticity is involved in affective-like behavioral changes observed in BD. These findings are leading to the development of novel therapeutics for this devastating illness.

Original languageEnglish
Pages (from-to)1160-1171
Number of pages12
JournalBiological Psychiatry
Issue number12
StatePublished - 15 Jun 2006
Externally publishedYes


  • Mania
  • cellular plasticity
  • underlying mechanisms

ASJC Scopus subject areas

  • Biological Psychiatry


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