Involvement of corticotropin-releasing factor in chronic stress regulation of the brain noradrenergic system.
Involvement of corticotropin-releasing factor in chronic stress regulation of the brain noradrenergic system.
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促肾上腺皮质激素释放因子参与大脑去甲肾上腺素能系统的慢性应激调节。
DOI：
10.1073/pnas.88.19.8382
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发表时间：
1991
影响因子：
11.1
通讯作者：
Duman,RS
中科院分区：
文献类型：
--
作者：
Melia,KR;Duman,RS
促肾上腺皮质激素释放因子（CRF）和去甲肾上腺素（NE）介导许多激素，自主神经和急性应激的行为效应，这些神经递质之间的相互作用可能是神经元适应慢性应激的基础。为了验证这一假设，慢性给药CRF和特定的CRF拮抗剂，α-螺旋CRF，对酪氨酸羟化酶，NE生物合成的限速酶的诱导的影响，在大鼠蓝斑（LC）进行了检查。我们现在报告说，管理的α-螺旋CRF特异性地阻断酪氨酸羟化酶的诱导，在一个重复的间歇性应激范式，涉及脚休克和噪音应激，但没有影响稳态水平的酶在非应激动物或诱导的酶在利血平治疗。此外，CRF单独重复给药5天，如慢性应激，增加了LC中酪氨酸羟化酶的水平。结果表明，内源性CRF是必要的诱导酪氨酸羟化酶在响应这种压力的范例和外源性管理CRF是足够的调节这种酶在非应激大鼠。这些发现可能证明在阐明慢性应激触发和维持与一些应激相关的精神疾病相关的生化改变的机制方面很重要。
Corticotropin-releasing factor (CRF) and norepinephrine (NE) mediate many hormonal, autonomic, and behavioral effects of acute stress, and it is possible that an interaction between these neurotransmitters could underlie neuronal adaptations in response to chronic stress. To test this hypothesis, the influence of chronically administered CRF and a specific CRF antagonist, alpha-helical CRF, on the induction of tyrosine hydroxylase, the rate-limiting enzyme in NE biosynthesis, was examined in the rat locus coeruleus (LC). We now report that administration of alpha-helical CRF specifically blocks the induction of tyrosine hydroxylase in response to a repeated intermittent stress paradigm involving foot shock and noise stress but has no effect on steady-state levels of the enzyme in nonstressed animals or on the induction of the enzyme in response to reserpine treatment. In addition, repeated administration of CRF alone for 5 days, like chronic stress, increases levels of tyrosine hydroxylase in LC. The results demonstrate that endogenous CRF is necessary for the induction of tyrosine hydroxylase in response to this stress paradigm and that exogenously administered CRF is sufficient for the regulation of this enzyme in nonstressed rats. These findings may prove important in elucidating mechanisms by which chronic stress triggers and sustains the biochemical alterations associated with some stress-related psychiatric disorders.