Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders

doi:10.1016/S0306-4522(02)00364-0

Neuroscience

Volume 115, Issue 1, 15 November 2002, Pages 229-242

https://doi.org/10.1016/S0306-4522(02)00364-0 Get rights and content

Abstract

The brain noradrenergic system is activated by stress, modulating the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress. In this study, we characterized brain noradrenergic reactivity to acute immobilization stress in three rat strains that differ in their neuroendocrine stress response: the inbred Lewis (Lew) and Wistar–Kyoto (WKY) rats, and outbred Sprague–Dawley (SD) rats. Noradrenergic reactivity was assessed by measuring tyrosine hydroxylase mRNA expression in locus coeruleus, and norepinephrine release in the lateral bed nucleus of the stria terminalis. Behavioral measures of arousal and acute stress responsivity included locomotion in a novel environment, fear-potentiated startle, and stress-induced reductions in social interaction and open-arm exploration on the elevated-plus maze. Neuroendocrine responses were assessed by plasma adrenocorticotropic hormone. Compared to SD, adrenocorticotropic hormone responses of Lew rats were blunted, whereas those of WKY were enhanced. The behavioral effects of stress were similar in Lew and SD rats, despite baseline differences. Lew had similar elevations of tyrosine hydroxylase mRNA, and initially greater norepinephrine release in the lateral bed nucleus of the stria terminalis during stress, although both noradrenergic responses returned toward baseline more rapidly than in SD rats. WKY rats showed depressed baseline startle and lower baseline exploratory and social behavior than SD. However, unlike the Lew or SD rats, WKY exhibited a lack both of fear potentiation of the startle response and of stress-induced reductions in exploratory and social behavior, indicating attenuated stress responsivity. Acute noradrenergic reactivity to stress, measured by either tyrosine hydroxylase mRNA levels or norepinephrine release, was also attenuated in WKY rats. Thus, reduced arousal and behavioral responsivity in WKY rats may be related to deficient brain noradrenergic reactivity. This deficit may alter their ability to cope with stress, resulting in the exaggerated neuroendocrine responses and increased susceptibility to stress-related pathology exhibited by this strain.

Section snippets

Animals

Adult male WKY, Lew or SD rats were obtained from Charles River (Raleigh, NC, USA). For most experiments, rats weighing 200–250 g upon arrival were allowed to acclimate to the animal facility for 7–10 days prior to use. The housing facility was maintained on a 12-h light cycle (lights on at 07.00 h). Experiments took place between 09.00 and 14.00 h. Animals initially were housed three per cage, all from the same strain, with ad libitum access to food and water. Four days prior to the beginning

Stress-induced ACTH secretion

Significant main effects of strain (F_(2,100)=26.34, P<0.0001), time (F_(3,100)=107.33, P<0.0001) and a strain×time interaction (F_(6,100)=8.31, P<0.0001) were observed on the neuroendocrine response to stress. In unstressed baseline samples, plasma ACTH in trunk blood was comparably low in all three strains. Acute immobilization stress induced a significant increase in plasma ACTH in all strains (P<0.01), which returned toward baseline levels over the course of the post-stress recovery period (

Discussion

In this study, we characterized brain noradrenergic reactivity to acute immobilization stress in three rat strains that differ in the degree of activation of the HPA axis in response to stress. We first verified the blunted HPA response to stress in Lew rats (Gomez et al., 1998, Sternberg et al., 1989) and the exaggerated response of WKY rats (Pare and Redei, 1993, Redei et al., 1994). Similar hyper-reactivity of the peripheral physiological response to stress in WKY rats has also been

Acknowledgements

Supported by research grants from NIMH (MH53851 to D.A.M.) and the Veterans Administration/Department of Defense. We thank Dr. Martin Javors, University of Texas Health Science Center at San Antonio, for HPLC analyses of microdialysate samples.

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Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders

Abstract

Section snippets

Animals

Stress-induced ACTH secretion

Discussion

Acknowledgements

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