Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
Int J Mol Sci. 2021 Mar 20;22(6):3189. doi: 10.3390/ijms22063189.
Nicotine is the predominant addictive compound of tobacco and causes the acquisition of dependence through its interactions with nicotinic acetylcholine receptors and various neurotransmitter releases in the central nervous system. The Ca/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) play a pivotal role in synaptic plasticity in the hippocampus. CaMKII is involved in long-term potentiation induction, which underlies the consolidation of learning and memory; however, the roles of CaMKII in nicotine and other psychostimulant-induced addiction still require further investigation. This article reviews the molecular mechanisms and crucial roles of CaMKII and ERK in nicotine and other stimulant drug-induced addiction. We also discuss dopamine (DA) receptor signaling involved in nicotine-induced addiction in the brain reward circuitry. In the last section, we introduce the association of polyunsaturated fatty acids and cellular chaperones of fatty acid-binding protein 3 in the context of nicotine-induced addiction in the mouse nucleus accumbens and provide a novel target for the treatment of drug abuse affecting dopaminergic systems.
尼古丁是烟草中主要的成瘾化合物，通过与烟碱型乙酰胆碱受体相互作用以及在中枢神经系统中释放各种神经递质，导致依赖性的产生。钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）和细胞外信号调节激酶（ERK）在海马体的突触可塑性中发挥关键作用。CaMKII 参与长时程增强诱导，这是学习和记忆巩固的基础；然而，CaMKII 在尼古丁和其他精神兴奋剂诱导的成瘾中的作用仍需要进一步研究。本文综述了 CaMKII 和 ERK 在尼古丁和其他兴奋剂诱导的成瘾中的分子机制和关键作用。我们还讨论了多巴胺（DA）受体信号在大脑奖励回路中尼古丁诱导成瘾中的作用。在最后一节中，我们介绍了多不饱和脂肪酸与脂肪酸结合蛋白 3 的细胞伴侣在尼古丁诱导的小鼠伏隔核成瘾中的关联，并为治疗影响多巴胺能系统的药物滥用提供了一个新的靶点。
