Pardon M-C, Gould G G, Garcia A, Phillips L, Cook M C, Miller S A, Mason P A, Morilak D A
Department of Pharmacology, University of Texas Health Science Center at San Antonio, MC 7764, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Neuroscience. 2002;115(1):229-42. doi: 10.1016/s0306-4522(02)00364-0.
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.
应激可激活大脑去甲肾上腺素能系统，调节前脑区域的活动，这些区域参与对应激的行为和神经内分泌反应。在本研究中，我们对三种在神经内分泌应激反应方面存在差异的大鼠品系——近交系Lewis（Lew）大鼠、Wistar-Kyoto（WKY）大鼠和远交系Sprague-Dawley（SD）大鼠——大脑去甲肾上腺素能对应激的反应性进行了表征。通过测量蓝斑中酪氨酸羟化酶mRNA的表达以及终纹床核外侧去甲肾上腺素的释放来评估去甲肾上腺素能反应性。觉醒和急性应激反应性的行为指标包括在新环境中的运动、恐惧增强的惊吓反应，以及应激诱导的社交互动减少和高架十字迷宫中开放臂探索减少。通过血浆促肾上腺皮质激素评估神经内分泌反应。与SD大鼠相比，Lew大鼠的促肾上腺皮质激素反应减弱，而WKY大鼠的则增强。尽管基线存在差异，但Lew和SD大鼠应激的行为效应相似。Lew大鼠的酪氨酸羟化酶mRNA有类似程度的升高，并且在应激期间终纹床核外侧的去甲肾上腺素释放最初更多，尽管两种去甲肾上腺素能反应都比SD大鼠更快地恢复到基线水平。WKY大鼠的基线惊吓反应较低，且基线探索和社交行为比SD大鼠少。然而，与Lew或SD大鼠不同，WKY大鼠既没有惊吓反应的恐惧增强，也没有应激诱导的探索和社交行为减少，表明其应激反应性减弱。通过酪氨酸羟化酶mRNA水平或去甲肾上腺素释放测量的急性去甲肾上腺素能对应激的反应性在WKY大鼠中也减弱。因此，WKY大鼠觉醒和行为反应性降低可能与大脑去甲肾上腺素能反应性不足有关。这种缺陷可能会改变它们应对应激的能力，导致该品系出现夸张的神经内分泌反应以及对应激相关病理的易感性增加。
