Busquets X, Ventayol P, García-Sevilla J A
Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain.
Brain Res Mol Brain Res. 1997 Apr;45(1):154-8. doi: 10.1016/s0169-328x(96)00307-5.
Opiate withdrawal has been associated with up-regulation of alpha 2-adrenoceptors (mainly the alpha 2A-subtype) in brain. The modulation of these inhibitory receptors regulating norepinephrine release appears to be a relevant mechanism by which the opiate abstinence syndrome might be counteracted. The aim of this study was to investigate possible changes in alpha 2a-adrenoceptor gene expression as the molecular mechanism underlying the opiate withdrawal-induced up-regulation of alpha 2A-adrenoceptors. In morphine-dependent rats (10-100 mg/kg for 5 days), naloxone (2 mg/kg)-precipitated withdrawal induced a rapid (2 h) and marked up-regulation (111%, P < 0.001) in the expression of alpha 2a-adrenoceptor mRNA (Northern and dot-blot analyses) in the cerebral cortex. Acute and chronic morphine treatments did not alter significantly the expression of cortical alpha 2a-adrenoceptor mRNA. The results indicate that the opiate abstinence syndrome is associated with a transcriptional activation of the alpha 2a-adrenoceptor mRNA which can explain the up-regulation of brain alpha 2A-adrenoceptors during opiate withdrawal.
阿片类药物戒断与大脑中α2-肾上腺素能受体（主要是α2A亚型）的上调有关。调节去甲肾上腺素释放的这些抑制性受体的调节似乎是一种相关机制，通过该机制可能抵消阿片类药物戒断综合征。本研究的目的是研究α2a-肾上腺素能受体基因表达的可能变化，作为阿片类药物戒断诱导的α2A-肾上腺素能受体上调的分子机制。在吗啡依赖大鼠（10 - 100 mg/kg，持续5天）中，纳洛酮（2 mg/kg）诱发的戒断在大脑皮层中诱导了α2a-肾上腺素能受体mRNA表达的快速（2小时）和显著上调（111%，P < 0.001）（Northern和斑点印迹分析）。急性和慢性吗啡处理并未显著改变皮层α2a-肾上腺素能受体mRNA的表达。结果表明，阿片类药物戒断综合征与α2a-肾上腺素能受体mRNA的转录激活有关，这可以解释阿片类药物戒断期间大脑α2A-肾上腺素能受体的上调。
