Altered regulation of CREB by chronic antidepressant administration in the brain of transgenic mice with impaired glucocorticoid receptor function

Neuropsychopharmacology. 2002 May;26(5):605-14. doi: 10.1016/S0893-133X(01)00401-8.


Various effects of antidepressant drugs on gene transcription have been described and altered gene expression has been proposed as being a common biological basis underlying depressive illness. One target for the common action of antidepressants is a modifying effect on the regulation of postreceptor pathways and genes related to the cAMP cascade. Recent studies have demonstrated that long-term antidepressant treatment resulted in sustained activation of the cyclic adenosine 3',5'-monophosphate system and in increased expression of the transcription factor cAMP response element binding protein (CREB). A transgenic animal model of depression with impaired glucocorticoid receptor function was used to investigate the effect of chronic antidepressant treatments on CREB expression in different brain areas. Wild-type and transgenic mice received one administration of saline, desipramine, or fluoxetine, daily for 21 days. The effects of antidepressants on CREB mRNA were analyzed using a sensitive RNase protection assay. Antidepressant treatment resulted in a neuroanatomically and animal specific expression pattern of CREB. Our findings suggest that life-long central glucocorticoid receptor dysfunction results in an altered sensitivity with respect to the effects of antidepressants on the expression of CREB.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage*
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain / physiology
  • Cyclic AMP Response Element-Binding Protein / biosynthesis
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / physiology
  • Receptors, Glucocorticoid / deficiency*
  • Receptors, Glucocorticoid / genetics*


  • Antidepressive Agents
  • Cyclic AMP Response Element-Binding Protein
  • RNA, Messenger
  • Receptors, Glucocorticoid