Journal
MOLECULAR PSYCHIATRY
Volume 8, Issue 4, Pages 423-433Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4001255
Keywords
heritability; forced swim behavior; hypothalamic-pituitary-adrenal axis; corticosterone; adrenal weight; stress response; strain differences; genetics
Funding
- NIMH NIH HHS [MH60789] Funding Source: Medline
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH060789] Funding Source: NIH RePORTER
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Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a proposed animal model of depression, the Wistar Kyoto (WKY) rat, to investigate the relationship as well as the mode of inheritance of FST behaviors and HPA measures. Through reciprocal breeding of WKY and F344 parent strains and brother sister breeding of the F1 generation, we obtained 486 F2 animals. Parent, F1 and F2 animals were tested in the FST. Blood samples were collected for determination of basal and stress (10-min restraint) plasma corticosterone (CORT) levels, and adrenal weights were measured. We found that all measures were heritable to some extent and that this heritability was highly sex dependent. Both correlation and factor analyses of the F2 generation data demonstrate that FST behavior and HPA axis measures are not directly related. Thus, the underlying genetic components of depressive-like behavior and HPA axis abnormalities are likely to be disparate in the segregating F2 generation of a WKYxF344 cross.
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