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首页> 外文期刊>The European Journal of Neuroscience >Enabling role of adenosine A1 receptors in adenosine A2A receptor-mediated striatal expression of c-fos.
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Enabling role of adenosine A1 receptors in adenosine A2A receptor-mediated striatal expression of c-fos.

机译：腺苷A1受体在腺苷A2A受体介导的c-fos纹状体表达中的促成作用。

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摘要

When striatal neurons are strongly activated they produce adenosine, which activates nearby adenosine A1 receptors (A1Rs) and adenosine A2A receptors (A2ARs). Although the effects of A1R or A2AR activation on neural activity in the striatum have been examined separately, the effects of coactivating both receptors has not been investigated. Using c-Fos immunohistochemistry as an indicator of neural activity, we examined the effects of coactivation of A1Rs and A2ARs on neural activity and their mechanism of interaction in the caudate-putamen, nucleus accumbens (NAc) and prefrontal cortex in rats. Administration of a motor-depressant dose of the A2AR agonist CGS 21680 (0.5 mg/kg i.p.) did not significantly induce c-fos expression in any of these brain regions. Administration of a motor-depressant dose of the A1R agonist CPA (0.3 mg/kg, i.p.) produced a small but significant induction of c-fos expression only in the shell of the NAc. Coadministration of CGS 21680 and CPA produced a synergistic induction ofc-fos expression in the caudate-putamen, cingulate cortex, and especially the NAc. In the shell of the NAc administration of CPA significantly decreased extracellular dopamine levels measured by in vivo microdialysis and blocked CGS 21680-induced increases in dopamine levels. Because it has been previously shown that activation of dopamine D2 receptors (D2Rs) by endogenous dopamine blocks A2AR-mediated c-fos expression, it is hypothesized that the enabling role of A1Rs in A2AR-mediated striatal c-fos expression is related to the A1R-mediated inhibition of dopamine release.
机译：当纹状体神经元被强烈激活时，它们会产生腺苷，从而激活附近的腺苷A1受体（A1Rs）和腺苷A2A受体（A2ARs）。尽管已经分别检查了A1R或A2AR激活对纹状体神经活动的影响，但尚未研究过共同激活两种受体的作用。使用c-Fos免疫组织化学作为神经活动的指标，我们检查了A1Rs和A2ARs共同激活对大鼠尾状-丘脑，伏伏核（NAc）和前额叶皮层神经活动及其相互作用机制的影响。给予抗抑郁药剂量的A2AR激动剂CGS 21680（0.5 mg / kg腹腔注射）在任何这些脑区域均未明显诱导c-fos表达。给予抗抑郁药剂量的A1R激动剂CPA（0.3 mg / kg，腹腔注射）仅在NAc的外壳中产生了c-fos表达的小而显着诱导。 CGS 21680和CPA的共同给药在尾状豆状体，扣带回皮层，尤其是NAc中协同诱导c-fos表达。在NAc的外壳中，通过体内微透析测量的CPA显着降低了细胞外多巴胺水平，并阻止了CGS 21680诱导的多巴胺水平升高。由于先前已经证明内源性多巴胺激活多巴胺D2受体（D2Rs）会阻断A2AR介导的c-fos表达，因此假设A1Rs在A2AR介导的纹状体c-fos表达中的促进作用与A1R相关介导的多巴胺释放抑制。

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