DigitalCommons@WayneState

Title

cAMP Response Element-Binding Protein Deficiency Allows for Increased Neurogenesis and a Rapid Onset of Antidepressant Response

Authors

Tamar L. Gur, University of Pennsylvania
Alana C. Conti, University of PennsylvaniaFollow
Jessica Holden, University of Pennsylvania
Anita J. Bechtholt, University of Pennsylvania
Tiffany E. Hill, University of Pennsylvania
Irwin Lucki, University of Pennsylvania
Jessica E. Malberg, Wyeth Research
Julie A. Blendy, University of Pennsylvania

Document Type

Article

Abstract

cAMP response element-binding protein (CREB) has been implicated in the molecular and cellular mechanisms of chronic antidepressant (AD) treatment, although its role in the behavioral response is unclear. CREB-deficient (CREB^αΔ mutant) mice demonstrate an antidepressant phenotype in the tail suspension test (TST) and forced-swim test. Here, we show that, at baseline, CREB^αΔ mutant mice exhibited increased hippocampal cell proliferation and neurogenesis compared with wild-type (WT) controls, effects similar to those observed in WT mice after chronic desipramine (DMI) administration. Neurogenesis was not further augmented by chronic DMI treatment in CREB^αΔ mutant mice. Serotonin depletion decreased neurogenesis in CREB^αΔ mutant mice toWTlevels, which correlated with a reversal of the antidepressant phenotype in the TST. This effect was specific for the reversal of the antidepressant phenotype in these mice, because serotonin depletion did not alter a baseline anxiety-like behavior in CREB mutant mice. The response to chronic AD treatment in the novelty-induced hypophagia (NIH) test may rely on neurogenesis. Therefore, we used this paradigm to evaluate chronic AD treatment in CREB mutant mice to determine whether the increased neurogenesis in these mice alters their response in the NIH paradigm. Whereas both WT and CREB^αΔ mutant mice responded to chronic AD treatment in the NIH paradigm, only CREB^αΔ mutant mice responded to acute AD treatment. However, in the elevated zero maze, DMI did not reverse anxiety behavior in mutant mice. Together, these data show that increased hippocampal neurogenesis allows for an antidepressant phenotype as well as a rapid onset of behavioral responses to AD treatment.

Comments

Copyright © 2007 Society for Neuroscience

Recommended Citation

Gur TL, Conti AC, Holden J, et al. cAMP response element-binding protein deficiency allows for increased neurogenesis and a rapid onset of antidepressant response. J Neurosci 2007;27:7860-68. doi:10.1523/JNEUROSCI.2051-07.2007