Beaulieu Jean-Martin, Gainetdinov Raul R, Caron Marc G
Department of Anatomy and Physiology, Université Laval/CRULRG, Québec, Canada.
Annu Rev Pharmacol Toxicol. 2009;49:327-47. doi: 10.1146/annurev.pharmtox.011008.145634.
Psychotropic drugs acting on monoamine neurotransmission are major pharmacological treatments for neuropsychiatric conditions such as schizophrenia, depression, bipolar disorder, Tourette syndrome, ADHD, and Alzheimer disease. Independent lines of research involving biochemical and behavioral approaches in normal and/or genetically modified mice provide converging evidence for an involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by dopamine and serotonin (5-HT). These signaling molecules have also received attention for their role in the actions of psychoactive drugs such as antidepressants, antipsychotics, lithium, and other mood stabilizers. Furthermore, investigations of the mechanism by which D2 dopamine receptors regulate Akt/GSK3 signaling strongly support the physiological relevance of a new modality of G protein-coupled receptor (GPCR) signaling involving the multifunctional scaffolding protein beta-arrestin 2. Elucidation of the contribution of multiple signaling pathways to the action of psychotropic drugs may provide a better biological understanding of psychiatric disorders and lead to more efficient therapeutics.
作用于单胺神经传递的精神药物是治疗精神疾病的主要药理学方法，这些精神疾病包括精神分裂症、抑郁症、双相情感障碍、妥瑞氏症、注意力缺陷多动障碍和阿尔茨海默病。在正常和/或基因改造小鼠中，涉及生化和行为学方法的独立研究系列为信号分子Akt和糖原合酶激酶-3（GSK3）参与多巴胺和5-羟色胺（5-HT）对行为的调节提供了一致的证据。这些信号分子在抗抑郁药、抗精神病药、锂盐和其他心境稳定剂等精神活性药物的作用中所起的作用也受到了关注。此外，对D2多巴胺受体调节Akt/GSK3信号传导机制的研究有力地支持了一种涉及多功能支架蛋白β-arrestin 2的G蛋白偶联受体（GPCR）信号传导新模式的生理相关性。阐明多种信号通路对精神药物作用的贡献，可能会为精神疾病提供更好的生物学理解，并带来更有效的治疗方法。
