Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides and receptors spans multiple PFC cell types and circuits, and this extensive opioid system has emerged as a key substrate underlying reward, motivation, affective behaviors, and adaptations to stress. Here, we review the current evidence for dysregulated cortical opioid signaling in the pathogenesis of psychiatric disorders. We begin by providing an introduction to the basic anatomy and function of the cortical opioid system, followed by a discussion of endogenous and exogenous opioid modulation of PFC function at the behavioral, cellular, and synaptic level. Finally, we highlight the therapeutic potential of endogenous opioid targets in the treatment of psychiatric disorders, synthesizing clinical reports of altered opioid peptide and receptor expression and activity in human patients and summarizing new developments in opioid-based medications.

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阿片类药物对前额皮质细胞和回路的调节

几种神经化学系统汇聚在前额皮质（PFC）中，以调节认知和动机行为。丰富的内源性阿片肽和受体网络跨越多种 PFC 细胞类型和回路，这种广泛的阿片系统已成为奖励、动机、情感行为和压力适应的关键底物。在这里，我们回顾了精神疾病发病机制中皮质阿片类信号传导失调的当前证据。我们首先介绍皮质阿片系统的基本解剖结构和功能，然后讨论内源性和外源性阿片类药物在行为、细胞和突触水平上对 PFC 功能的调节。最后，我们强调了内源性阿片类药物靶点在精神疾病治疗中的治疗潜力，综合了人类患者中阿片类肽和受体表达和活性改变的临床报告，并总结了基于阿片类药物的新进展。