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首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control thepituitary-adrenocortical axis in rats
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Effects of morphine and morphine withdrawal on brainstem neurons innervating hypothalamic nuclei that control thepituitary-adrenocortical axis in rats

机译：吗啡和吗啡戒断对大鼠下丘脑核控制脑垂体-肾上腺皮质轴的脑干神经元的影响

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class="enumerated" style="list-style-type:decimal">Different data support a role for brainstem noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) in the control of hypothalamus – pituitary – adrenocortical (HPA) axis. However, little is known regarding the functional adaptive changes of noradrenergic afferent innervating the PVN and supraoptic nucleus (SON) during chronic opioid exposure and upon morphine withdrawal.Here we have studied the expression of Fos after administration of morphine and during morphine withdrawal in the rat hypothalamic PVN and SON. Fos production was also studied in brainstem regions that innervate hypothalamic nuclei: the nucleus of solitary tract (NTS – A2) and the ventrolateral medulla (VLM – A1) and combined with immunostaining for tyrosine hydroxylase (TH) for immunohistochemical identification of active neurons during morphine withdrawal. Male rats were implanted with s.c. placebo or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received an injection of saline i.p., morphine i.p., saline s.c. or naloxone s.c.Acute morphine administration produced an increase in Fos expression at hypothalamic nuclei and in the brainstem regions, and tolerance developed towards this effect. Precipitated morphine withdrawal induced marked Fos immunoreactivity within the PVN and SON. Concomitantly, numerous neurons in the brainstem were stimulated by morphine withdrawal. Moreover, catecholaminergic-positive neurons in the brainstem showed a significant increase in Fos expression in response to morphine withdrawal.These findings demonstrate that chronic activation of opioid receptors results in altered patterns of immediate-early genes (IEG) expression in the PVN and SON, which occurs concurrently with an increased activity of their inputs from the brainstem.
机译：class =“ enumerated” style =“ list-style-type：decimal”> <！-list-behavior =枚举前缀-word = mark-type = decimal max-label-size = 0-> 不同的数据支持脑干去甲肾上腺素能输入到下丘脑室旁核（PVN）在控制下丘脑－垂体－肾上腺皮质（HPA）轴中的作用。然而，关于在慢性阿片类药物暴露和吗啡戒断后去甲肾上腺素能传入神经神经元和视上核（SON）的功能适应性变化知之甚少。 在此我们研究了吗啡给药后Fos的表达在大鼠下丘脑PVN和SON中吗啡戒断期间。在下丘脑神经支配的脑干区域也研究了Fos的产生：孤束核（NTS – A2）和腹侧延髓（VLM – A1）的核仁，并与酪氨酸羟化酶（TH）的免疫染色结合用于吗啡期间活性神经元的免疫组织化学鉴定退出。雄性大鼠植入s.c.安慰剂或吗啡（耐受性/依赖性）药丸持续7天。在第8天，给大鼠注射生理盐水，吗啡，生理盐水。或服用纳洛酮 急性吗啡使下丘脑核和脑干区域的Fos表达增加，并且对这种作用产生了耐受性。沉淀的吗啡戒断可在PVN和SON内引起明显的Fos免疫反应性。伴随地，吗啡戒断刺激了脑干中的许多神经元。此外，脑干中的儿茶酚胺能阳性神经元响应吗啡戒断显示Fos表达显着增加。 这些发现表明，阿片受体的长期激活会导致即早基因（IEG）的模式改变。在PVN和SON中表达，这与脑干的输入活动增加同时发生。

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