Karcz-Kubicha Marzena, Ferré Sergi, Díaz-Ruiz Oscar, Quiroz-Molina César, Goldberg Steven R, Hope Bruce T, Morales Marisela
Behavioral Neuroscience Branch, National Institute on Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224, USA.
Neuropsychopharmacology. 2006 Oct;31(10):2173-9. doi: 10.1038/sj.npp.1301035. Epub 2006 Feb 1.
In the striatum, adenosine A2A and dopamine D2 receptors exert reciprocal antagonistic interactions that modulate the function of GABAergic enkephalinergic neurons. We have previously shown that stimulation of adenosine A1 receptors allows the stimulation of A2A receptors to overcome a tonic inhibitory effect of D2 receptors and induce striatal expression of c-fos. In the present work, by studying co-localization of c-Fos immunoreactivity and preproenkephalin and preprodynorphin transcripts, we show that co-administration of the A1 receptor agonist CPA and the A2A receptor agonist CGS 21680 increases the striatal expression of c-fos in GABAergic enkephalinergic but not in GABAergic dynorphinergic neurons. Co-administration of CPA and CGS 21680 also induced a significant increase in the striatal expression of preproenkephalin. The results underscore the role of adenosine in the activation of gene expression in the GABAergic enkephalinergic neuron.
在纹状体中，腺苷A2A受体和多巴胺D2受体发挥相互拮抗作用，调节γ-氨基丁酸能脑啡肽能神经元的功能。我们之前已经表明，刺激腺苷A1受体可使A2A受体的刺激克服D2受体的紧张性抑制作用，并诱导纹状体中c-fos的表达。在本研究中，通过研究c-Fos免疫反应性与前脑啡肽原和前强啡肽原转录本的共定位，我们发现A1受体激动剂CPA和A2A受体激动剂CGS 21680联合给药可增加γ-氨基丁酸能脑啡肽能神经元而非γ-氨基丁酸能强啡肽能神经元中纹状体c-fos的表达。CPA和CGS 21680联合给药还显著增加了前脑啡肽原在纹状体中的表达。这些结果强调了腺苷在γ-氨基丁酸能脑啡肽能神经元基因表达激活中的作用。
