Contet Candice, Kieffer Brigitte L, Befort Katia
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, UMR7104, Parc d'Innovation, 1 rue Laurent Fries BP 10142, 67404 Illkirch Cedex, Strasbourg, France.
Curr Opin Neurobiol. 2004 Jun;14(3):370-8. doi: 10.1016/j.conb.2004.05.005.
Mu opioid receptors mediate positive reinforcement following direct (morphine) or indirect (alcohol, cannabinoids, nicotine) activation, and our understanding of mu receptor function is central to the development of addiction therapies. Recent data obtained in native neurons confirm that mu receptor signaling and regulation are strongly agonist-dependent. Current functional mapping reveals morphine-activated neurons in the extended amygdala and early genomic approaches have identified novel mu receptor-associated proteins. A classification of about 30 genes either promoting or counteracting the addictive properties of morphine is proposed from the analysis of knockout mice data. The targeting of effectors or regulatory proteins, beyond the mu receptor itself, might provide valuable strategies to treat addictive disorders.
μ阿片受体在直接(吗啡)或间接(酒精、大麻素、尼古丁)激活后介导正性强化作用,而我们对μ受体功能的理解是成瘾治疗发展的核心。在天然神经元中获得的最新数据证实,μ受体信号传导和调节强烈依赖于激动剂。目前的功能图谱揭示了在杏仁核扩展区中被吗啡激活的神经元,并且早期的基因组学方法已经鉴定出与μ受体相关的新蛋白。通过对基因敲除小鼠数据的分析,提出了约30个促进或对抗吗啡成瘾特性的基因分类。针对μ受体本身之外的效应器或调节蛋白,可能为治疗成瘾性疾病提供有价值的策略。