Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53233, USA.
Department of Anesthesiology and Perioperative Medicine, Penn State College of Medicine, Hershey, PA 17033, USA; Departments of Neuroscience and Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Trends Pharmacol Sci. 2018 Mar;39(3):276-294. doi: 10.1016/j.tips.2017.12.004. Epub 2018 Jan 12.
Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system. We discuss adaptations in presynaptic/postsynaptic and extrasynaptic glutamate signaling produced by opioids and psychostimulants, and their relevance to circuit remodeling and addiction-related behavior - arguing that these core neural adaptations are important targets for developing pharmacotherapies to treat addiction to multiple drugs.
成瘾行为的共同特征，如渴望、刺激驱动的药物寻求以及戒断后高度易复发，促使人们提出了一种涵盖大多数滥用物质的统一成瘾理论。最近，这种单一理论受到了挑战，其依据是结构神经可塑性、生化信号和神经回路的差异，认为阿片类药物和精神兴奋剂成瘾在行为和神经生物学上是不同的。最近对药物诱导的可塑性的更选择性研究表明，这两类药物通过改变伏隔核中的兴奋性突触来促进总体奖励回路信号的重叠，伏隔核是奖励系统的关键组成部分。我们讨论了阿片类药物和精神兴奋剂引起的突触前/后和突触外谷氨酸信号传递的适应性，以及它们与回路重塑和与成瘾相关的行为的相关性，认为这些核心神经适应性是开发治疗多种药物成瘾的药物治疗的重要靶点。
