Maldonado R, Blendy J A, Tzavara E, Gass P, Roques B P, Hanoune J, Schütz G
Département de Pharmacochimie Moléculaire et Structurale, Unité de Recherche Associée D1500 CNRS, Université René Descartes, Faculté de Pharmacie, Paris, France.
Science. 1996 Aug 2;273(5275):657-9. doi: 10.1126/science.273.5275.657.
Chronic morphine administration induces an up-regulation of several components of the cyclic adenosine 5'-monophosphate (cAMP) signal transduction cascade. The behavioral and biochemical consequences of opiate withdrawal were investigated in mice with a genetic disruption of the alpha and Delta isoforms of the cAMP-responsive element-binding protein (CREB). In CREBalphadelta mutant mice the main symptoms of morphine withdrawal were strongly attenuated. No change in opioid binding sites or in morphine-induced analgesia was observed in these mutant mice, and the increase of adenylyl cyclase activity and immediate early gene expression after morphine withdrawal was normal. Thus, CREB-dependent gene transcription is a factor in the onset of behavioral manifestations of opiate dependence.
长期给予吗啡会导致环磷酸腺苷（cAMP）信号转导级联反应的几个组成部分上调。在cAMP反应元件结合蛋白（CREB）的α和δ亚型发生基因破坏的小鼠中，研究了阿片类药物戒断的行为和生化后果。在CREBαδ突变小鼠中，吗啡戒断的主要症状明显减轻。在这些突变小鼠中，未观察到阿片类结合位点或吗啡诱导的镇痛作用有变化，且吗啡戒断后腺苷酸环化酶活性和即刻早期基因表达的增加是正常的。因此，CREB依赖的基因转录是阿片类药物依赖行为表现发生的一个因素。
