Tipps Megan E, Buck Kari J
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA; Portland Alcohol Research Center, Portland VA Medical Center, Portland, Oregon, USA.
Int Rev Neurobiol. 2015;123:239-77. doi: 10.1016/bs.irn.2015.05.012.
The ability of drug-associated cues to reinitiate drug craving and seeking, even after long periods of abstinence, has led to the hypothesis that addiction represents a form of pathological learning, in which drugs of abuse hijack normal learning and memory processes to support long-term addictive behaviors. In this chapter, we review evidence suggesting that G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels are one mechanism through which numerous drugs of abuse can modulate learning and memory processes. We will examine the role of GIRK channels in two forms of experience-dependent long-term changes in neuronal function: homeostatic plasticity and synaptic plasticity. We will also discuss how drug-induced changes in GIRK-mediated signaling can lead to changes that support the development and maintenance of addiction.
即使经过长时间的戒断,与药物相关的线索仍有重新引发药物渴望和觅药行为的能力,这引发了一种假说,即成瘾代表一种病理性学习形式,其中滥用药物劫持正常的学习和记忆过程以支持长期成瘾行为。在本章中,我们回顾了相关证据,这些证据表明G蛋白门控内向整流钾(GIRK/Kir3)通道是众多滥用药物能够调节学习和记忆过程的一种机制。我们将研究GIRK通道在神经元功能的两种经验依赖性长期变化形式中的作用:稳态可塑性和突触可塑性。我们还将讨论药物诱导的GIRK介导信号变化如何导致支持成瘾发展和维持的变化。