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Inhibition of orexin receptor 1 contributes to the development of morphine dependence via attenuation of cAMP response element-binding protein and phospholipase Cβ3
Journal of Chemical Neuroanatomy ( IF 2.8 ) Pub Date : 2020-10-01 , DOI: 10.1016/j.jchemneu.2020.101801
Masoumeh Kourosh-Arami 1 , Mohammad Javan 2 , Saeed Semnanian 2
Affiliation  

Noradrenergic neurons of the locus coeruleus (LC) receive projection from hypothalamus orexinergic neurons and express orexin 1 receptor (Orx1). Orx in the locus coeruleus nucleus is involved in the development of morphine dependence. The downstream signaling of Orx contribution to the development of morphine dependence in LC neurons of morphine-dependent rats was studied. Therefore, we evaluated cyclic adenosine monophosphate (cAMP), cAMP response element-binding protein (CREB) and phospholipase Cβ3 (PLCβ3) levels by the application of immunohistochemistry. Results showed that cAMP, CREB and PLCβ3 levels were suppressed by the application of SB-334867 (as a selective Orx1 antagonist) in morphine-dependent rats. Our results unraveled that Orx1 blockade is involved in the development of morphine dependency through diminution of a variety of intracellular events including the cAMP, CREB and PLCβ3 levels in morphine-dependent rats. Furthermore, the Orx1 blockade could decrease the percentage of tyrosine hydroxylase (TH)+/CREB+ and TH+/PLCβ3+ neurons in LC of morphine-treated rats. It is concluded that the activation of Orx1 in LC nucleus might be involved in some intracellular changes in morphine dependent rats.

中文翻译:

抑制食欲素受体 1 通过减弱 cAMP 反应元件结合蛋白和磷脂酶 Cβ3 促进吗啡依赖性的发展

蓝斑 (LC) 的去甲肾上腺素能神经元接受下丘脑食欲素能神经元的投射并表达食欲素 1 受体 (Orx1)。蓝斑核中的 Orx 参与吗啡依赖的发展。研究了 Orx 对吗啡依赖大鼠 LC 神经元中吗啡依赖发展的下游信号传导。因此,我们通过应用免疫组织化学评估了环磷酸腺苷 (cAMP)、cAMP 反应元件结合蛋白 (CREB) 和磷脂酶 Cβ3 (PLCβ3) 的水平。结果表明,在吗啡依赖性大鼠中应用 SB-334867(作为选择性 Orx1 拮抗剂)可抑制 cAMP、CREB ​​和 PLCβ3 水平。我们的结果表明,Orx1 阻断通过减少吗啡依赖大鼠中的 cAMP、CREB ​​和 PLCβ3 水平等多种细胞内事件,参与了吗啡依赖的发展。此外,Orx1 阻断可以降低吗啡治疗大鼠 LC 中酪氨酸羟化酶 (TH)+/CREB+ 和 TH+/PLCβ3+ 神经元的百分比。结论LC细胞核中Orx1的激活可能与吗啡依赖大鼠的一些细胞内变化有关。
更新日期:2020-10-01
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