Opioid modulation of prefrontal cortex cells and circuits

Abstract

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. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Keywords: Addiction; Electrophysiology; G protein-coupled receptor (GPCR); Interneurons; Plasticity; Rodent models.

Figure 1.. Cell type-specific expression of cortical opioid receptors and peptides.

Cortex-wide receptor and peptide expression patterns were reconstructed from studies reporting discrete brain regions and cell types. Note that the absence of a peptide or receptor in this diagram does not necessarily indicate complete lack of cortical expression. Peptide/receptor symbols represent mRNA, gene, or protein expression. A) MOR and Enk expression. B) DOR and Enk expression. C) KOR and Dyn expression. Data obtained from: (Taki et al., 2000)¹; (Smith et al., 2019)²; (Jiang et al., 2021)³; (Zamfir et al., 2023)⁴; (Lau et al., 2020)⁵; (Birdsong et al., 2019)^6; (Pina et al., 2020)⁷; (Yarur et al., 2022)⁸; (Sohn et al., 2014)⁹. Sections of cortex are compressed along the anterior-posterior axis for stylistic purposes.