Depressive-like behavior and stress reactivity are independent traits in a Wistar Kyoto × Fisher 344 cross

Abstract

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 WKY3F344 cross.

Selectively bred Wistar–Kyoto rats: an animal model of depression and hyper-responsiveness to antidepressants

“…Further, WLI males had a higher plasma CORT response to restraint stress than WMI males, in agreement with our previous findings that 'normal' F344 males have a higher plasma CORT response to the same restraint stress than 'depressed' WKY males. 25 Although elevated HPA activity has been thought to be associated with depression, recent reports have found no such correlation in animal models. 25,32 Further, it has been reported that depressed patient subtypes can show either increased or decreased HPA activity.…”

“…25 Although elevated HPA activity has been thought to be associated with depression, recent reports have found no such correlation in animal models. 25,32 Further, it has been reported that depressed patient subtypes can show either increased or decreased HPA activity. 33 Several other rat lines have been selectively bred based on behavioral paradigms, usually starting with outbred populations.…”

“…25 At testing, rats were placed individually in a glass tank (30 cm  45 cm) of water (251C) for 15 min. After 24 h, rats were once again placed in the tank for a 5 min period.…”

Behavioral deficits associated with fetal alcohol exposure are reversed by prenatal thyroid hormone treatment: a role for maternal thyroid hormone deficiency in FAE

“…The FST procedure used was described previously. 45 Briefly, animals were placed into a glass cylinder (30 cm diameter, 45 cm deep) of 251C tap water for 15 min. After 24 h, rats were again placed into the cylinder of water for 5 min.…”

“…All testing took place between 1100 and 1500 h. Activity during the second swim test was video-recorded for subsequent scoring using a time-sampling technique previously described 46 in which behavior was scored as immobility, climbing, or swimming every 5 s. We have previously shown that immobility in the FST is not related to body weight. 45 Morris water maze At 80-90 days of age, minimum 20 days after the FST, the hidden platform version of the Morris water maze (MWM) was used to assess spatial learning. We chose not to administer a 'visual cue' version of the water maze for the following reasons.…”