Wen Rui-Ting, Feng Wan-Yu, Liang Jian-Hui, Zhang Han-Ting
National Institute on Drug Dependence, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, P. R. China.
Curr Pharm Des. 2015;21(3):355-64. doi: 10.2174/1381612820666140826114412.
The harmful effects caused by misuse of psychoactive substances have raised both medical and social problems. Substance dependence is a chronic relapsing disorder, which appears to involve neuroadaptive changes in cellular signaling and downstream gene expression. The unchanged consumption of present substances and increasing demand for new psychostimulants make the development of novel management/treatment strategies challenging. Emerging evidence has shown that the cyclic AMP (cAMP) signaling cascade plays a critical role in the initiation and development of dependence. Thus, phosphodiesterase 4 (PDE4), the primary hydrolytic enzyme for intracellular cAMP, is considered a potential target for future therapeutics dealing with prevention and intervention of substance dependence. This implication is supported by recent data from preclinical studies, and the rapid development of PDE4 inhibitors. Taken together, specific inhibitors of PDE4 and its subtypes possibly represent a novel class of pharmacotherapies for the prevention and abstinence of substance dependence. Here we discuss the modulatory role of cAMP signal transduction in the process of substance dependence and highlight recent evidence that PDE4 inhibitors might be a promising approach to substance dependence therapy.
精神活性物质的滥用所造成的有害影响引发了医学和社会问题。物质依赖是一种慢性复发性疾病，似乎涉及细胞信号传导和下游基因表达中的神经适应性变化。现有物质的持续消费以及对新型精神兴奋剂的需求不断增加，使得开发新的管理/治疗策略具有挑战性。新出现的证据表明，环磷酸腺苷（cAMP）信号级联在依赖的起始和发展中起关键作用。因此，细胞内cAMP的主要水解酶磷酸二酯酶4（PDE4）被认为是未来用于预防和干预物质依赖的治疗的潜在靶点。临床前研究的最新数据以及PDE4抑制剂的快速发展支持了这一观点。综上所述，PDE4及其亚型的特异性抑制剂可能代表了一类用于预防和戒除物质依赖的新型药物疗法。在此，我们讨论cAMP信号转导在物质依赖过程中的调节作用，并强调最近的证据表明PDE4抑制剂可能是物质依赖治疗的一种有前景的方法。
