Behavioral effects of Bcl-2 deficiency: Implications for affective disorders

Renae Lien, Shlomit Flaisher-Grinberg, Caitlin Cleary, Megan Hejny, Haim Einat

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


New hypotheses regarding affective disorders suggest a critical role for cellular resilience and plasticity. Bcl-2 is a central protein in these processes and is elevated by mood stabilizers and antidepressants. In previous studies, mice with targeted mutations of Bcl-2 showed anxiety-related behavioral changes. The present study further explored the relationship between Bcl-2 and behavior using mice with a targeted mutation but with a different background strain than previously tested. Bcl-2 heterozygous mice (B6; 129S2-Bcl-2<tm 1 Sjk>/J) were tested in models of depression, mania and anxiety. Compared to Wild Type (WT) controls, mutant mice showed behaviors modeling two facets of mania: increased reward seeking and amphetamine sensitization. Moreover, the sensitization was attenuated by chronic pretreatment with lithium. In contrast to previous data, the mutation did not affect measures of anxiety. Although data are still minimal, it supports additionat-studies of the role of Bcl-2 in affective and anxiety disorders. The importance of background strain in behavioral phenotypes of mutant mice is known and the current lack of effect on anxiety measures may be related to high baseline anxiety of WT animals. More precise studies of Bcl-2 in affective and anxiety disorders will be possible when specific pharmacological modulators of Bcl-2 become available.

Original languageEnglish
Pages (from-to)490-498
Number of pages9
JournalPharmacological Reports
Issue number4
StatePublished - 1 Jan 2008
Externally publishedYes


  • Animal models
  • Bc1 proteins
  • Bipolar disorder
  • Depression
  • Mania

ASJC Scopus subject areas

  • Pharmacology


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