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- Title
Transient Early-Life Forebrain Corticotropin-Releasing Hormone Elevation Causes Long-Lasting Anxiogenic and Despair-Like Changes in Mice.
- Authors
Kolber, Benedict J.; Boyle, Maureen P.; Wieczorek, Lindsay; Kelley, Crystal L.; Onwuzurike, Chiamaka C.; Nettles, Sabin A.; Vogt, Sherri K.; Muglia, Louis J.
- Abstract
During development, early-life stress, such as abuse or trauma, induces long-lasting changes that are linked to adult anxiety and depressive behavior. It has been postulated that altered expression of corticotropin-releasing hormone (CRH) can at least partially account for the various effects of stress on behavior. In accord with this hypothesis, evidence from pharmacological and genetic studies has indicated the capacity of differing levels of CRH activity in different brain areas to produce behavioral changes. Furthermore, stress during early life or adulthood causes an increase in CRH release in a variety of neural sites. To evaluate the temporal and spatial specificity of the effect of early-life CRH exposure on adult behavior, the tetracycline-off system was used to produce mice with forebrain-restricted inducible expression of CRH. After transient elevation of CRH during development only, behavioral testing in adult mice revealed a persistent anxiogenic and despair-like phenotype. These behavioral changes were not associated with alterations in adult circadian or stress induced corticosterone release but were associated with changes in CRH receptor type 1 expression. Furthermore, the despair-like changes were normalized with antidepressant treatment. Overall, these studies suggest that forebrain-restricted CRH signaling during development can permanently alter stress adaptation leading to increases in maladaptive behavior in adulthood.
- Subjects
CORTICOTROPIN releasing hormone; GENOTYPE-environment interaction; LABORATORY mice; PHENOTYPES; ANTIDEPRESSANTS
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 7, p2571
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4470-09.2010