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前额皮质中α-肾上腺素受体的激活和阻断调节半帕金森病大鼠的焦虑样行为。

Activation and blockade of α-adrenoceptors in the prelimbic cortex regulate anxiety-like behaviors in hemiparkinsonian rats.

机构信息

Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

出版信息

Biochem Biophys Res Commun. 2019 Nov 19;519(4):697-704. doi: 10.1016/j.bbrc.2019.09.038. Epub 2019 Sep 19.

Abstract

At present, whether α-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related anxiety is unclear. We examined the effects of PrL α-adrenoceptors on anxiety-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Compared to the sham operation, the lesion induced anxiety-like responses as measured by the open field test and elevated plus-maze test. Intra-PrL injection of the α-adrenoceptor agonist clonidine (1.25, 2.5 or 5 μg/rat) produced anxiolytic effects in sham-operated and lesioned rats. Furthermore, intra-PrL injection of the α-adrenoceptor antagonist idazoxan (1, 2 or 4 μg/rat) induced anxiogenic effects in two groups of rats. The effective doses produced by clonidine and idazoxan in lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of clonidine (5 μg/rat) or idazoxan (4 μg/rat) decreased or increased dopamine (DA) and noradrenaline (NA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) and amygdala in sham-operated and lesioned rats, respectively. These results suggest that α-adrenoceptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in DA, NA and 5-HT levels in the mPFC and amygdala after activation and blockade of α-adrenoceptors.

摘要

目前,前额皮质(PrL)中的α-肾上腺素受体是否参与帕金森病相关焦虑尚不清楚。我们研究了 PrL 中的α-肾上腺素受体对内侧前脑束单侧 6-羟多巴胺损伤大鼠焦虑样行为的影响。与假手术相比,损伤诱导了旷场试验和高架十字迷宫试验中的焦虑样反应。与假手术组相比,PrL 内注射α-肾上腺素受体激动剂可乐定(1.25、2.5 或 5μg/大鼠)在假手术和损伤大鼠中产生了抗焦虑作用。此外,PrL 内注射α-肾上腺素受体拮抗剂伊达唑兰(1、2 或 4μg/大鼠)在两组大鼠中引起了焦虑作用。可乐定和伊达唑兰在损伤大鼠中产生的有效剂量高于假手术大鼠。神经化学结果表明,PrL 内注射可乐定(5μg/大鼠)或伊达唑兰(4μg/大鼠)分别降低或增加了假手术和损伤大鼠中内侧前额皮质(mPFC)和杏仁核中的多巴胺(DA)、去甲肾上腺素(NA)和 5-羟色胺(5-HT)水平。这些结果表明,PrL 中的α-肾上腺素受体参与了焦虑样行为的调节,这归因于激活和阻断α-肾上腺素受体后 mPFC 和杏仁核中 DA、NA 和 5-HT 水平的变化。

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