QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.093948v1 316/2/926    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, M.-K. Articles by Alkon, D. L. Search for Related Content PubMed PubMed Citation Articles by Sun, M.-K. Articles by Alkon, D. L. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Depression Hazardous Substances DB IMIPRAMINE

BEHAVIORAL PHARMACOLOGY

Differential Gender-Related Vulnerability to Depression Induction and Converging Antidepressant Responses in Rats

Blanchette Rockefeller Neurosciences Institute, Rockville, Maryland

Vulnerability of females to depression among humans has not previously been reflected in animal models. Here, we show, by using a novel animal model of depression, that young female Wistar rats are clearly more vulnerable to depression induction than the males. This differential female vulnerability follows estrous cycle stages, is associated with cognitive impairment, and can be markedly transformed with sex hormones. Male hormone reduces vulnerability in females, whereas female hormone increases vulnerability in males. The induced depressive behavior in both sexes, however, is sensitive to imipramine and to the antagonism of the glucocorticoid receptors within a hormonal pathway previously implicated in human depression. Anisomycin, a protein synthesis inhibitor, eliminates the antidepressive effects of both antidepressants and male hormone but does not affect depression induction and estradiol-induced higher vulnerability. Moreover, direct cerebroventricular administration of brain-derived neurotrophic factor (BDNF), whose mRNA levels in the hippocampus and frontal cortex reach its lowest levels when estrogen levels are highest, is sufficient to rescue the antidepressive effects in the presence of the protein synthesis inhibitor. A selective enhancement of BDNF expression and/or BDNF signal cascades in the neural circuits controlling mood may represent an effective strategy for the development of novel antidepressants for both sexes, whereas blocking the gender-related higher vulnerability to potentially depressogenic events may lead to the development of specific antidepressants for the females.

This article has been cited by other articles:

				M Ebinger, C Sievers, D Ivan, H. Schneider, and G. Stalla Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression? J Psychopharmacol, September 1, 2009; 23(7): 841 - 853. [Abstract] [PDF]

				Y. Lin, G. J. Ter Horst, R. Wichmann, P. Bakker, A. Liu, X. Li, and C. Westenbroek Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats Cereb Cortex, September 1, 2009; 19(9): 1978 - 1989. [Abstract] [Full Text] [PDF]

				A. Walf, C. Koonce, and C. Frye Adult female wildtype, but not oestrogen receptor {beta} knockout, mice have decreased depression-like behaviour during pro-oestrus and following administration of oestradiol or diarylpropionitrile J Psychopharmacol, June 1, 2009; 23(4): 442 - 450. [Abstract] [PDF]

				Y. Lin, C. Westenbroek, P. Bakker, J. Termeer, A. Liu, X. Li, and G. J. Ter Horst Effects of Long-Term Stress and Recovery on the Prefrontal Cortex and Dentate Gyrus in Male and Female Rats Cereb Cortex, December 1, 2008; 18(12): 2762 - 2774. [Abstract] [Full Text] [PDF]