Gonçalves Joana, Martins João, Baptista Sofia, Ambrósio António Francisco, Silva Ana Paula
Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Portugal.
Institute for Biomedical Imaging and Life Sciences (IBILI), University of Coimbra, Portugal.
Addict Biol. 2016 Jul;21(4):755-65. doi: 10.1111/adb.12250. Epub 2015 Apr 22.
Neuropeptide Y (NPY), which is widely expressed in the central nervous system is involved in several neuropathologies including addiction. Here we comprehensively and systematically review alterations on the central NPY system induced by several drugs. We report on the effects of psychostimulants [cocaine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and nicotine], ethanol, and opioids on NPY protein levels and expression of different NPY receptors. Overall, expression and function of NPY and its receptors are changed under conditions of drug exposure, thus affecting several physiologic behaviors, such as feeding, stress and anxiety. Drugs of abuse differentially affect the components of the NPY system. For example methamphetamine and nicotine lead to a consistent increase in NPY mRNA and protein levels in different brain sites whereas ethanol and opioids decrease NPY mRNA and protein expression. Drug-induced alterations on the different NPY receptors show more complex regulation pattern. Manipulation of the NPY system can have opposing effects on reinforcing and addictive properties of drugs of abuse. NPY can produce pro-addictive effects (nicotine and heroin), but can also exert inhibitory effects on addictive behavior (AMPH, ethanol). Furthermore, NPY can act as a neuroprotective agent in chronically methamphetamine and MDMA-treated rodents. In conclusion, manipulation of the NPY system seems to be a potential target to counteract neural alterations, addiction-related behaviors and cognitive deficits induced by these drugs.
神经肽Y（NPY）在中枢神经系统中广泛表达，参与包括成瘾在内的多种神经病理学过程。在此，我们全面且系统地综述了几种药物对中枢NPY系统的影响。我们报告了精神兴奋剂[可卡因、苯丙胺、甲基苯丙胺、3,4-亚甲基二氧基甲基苯丙胺（摇头丸）和尼古丁]、乙醇和阿片类药物对NPY蛋白水平及不同NPY受体表达的影响。总体而言，在药物暴露条件下，NPY及其受体的表达和功能会发生改变，从而影响多种生理行为，如进食、应激和焦虑。滥用药物对NPY系统的组成部分有不同影响。例如，甲基苯丙胺和尼古丁会导致不同脑区的NPY mRNA和蛋白水平持续升高，而乙醇和阿片类药物则会降低NPY mRNA和蛋白表达。药物引起的不同NPY受体的改变呈现出更复杂的调控模式。对NPY系统的调控可能对滥用药物的强化和成瘾特性产生相反的影响。NPY可产生促成瘾作用（尼古丁和海洛因），但也可对成瘾行为发挥抑制作用（苯丙胺、乙醇）。此外，在长期接受甲基苯丙胺和摇头丸治疗的啮齿动物中，NPY可作为一种神经保护剂。总之，对NPY系统的调控似乎是对抗这些药物引起的神经改变、成瘾相关行为和认知缺陷的潜在靶点。
