Friuli Marzia, Eramo Barbara, Sepe Christian, Kiani Mitra, Casolini Paola, Zuena Anna Rita
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy.
Physiol Behav. 2025 Jul 1;296:114929. doi: 10.1016/j.physbeh.2025.114929. Epub 2025 Apr 22.
Natural rewards such as food, mating, and social interaction are essential for survival and species preservation, and their regulation involves a complex interplay of motivational, cognitive, and emotional processes. Over the past two decades, increasing attention has been directed toward the endocannabinoid system and its paracannabinoid counterpart as key modulators of these behaviors. This review aims to provide an integrated overview of the roles played by the endocannabinoid and paracannabinoid systems in regulating natural reward-driven behaviors, focusing on feeding, reproductive behavior, and social interaction. We highlight how the endocannabinoid system - mainly through CB1 receptor signaling - modulates central and peripheral circuits involved in energy homeostasis, reward processing, and emotional regulation. In parallel, we explore the role of paracannabinoids, such as oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA), which act primarily via non-cannabinoid receptors and contribute to the regulation of appetite, sexual motivation, and social behavior. Special attention is given to the relevance of these systems in the pathophysiology of obesity, eating disorders, sexual dysfunctions, and social impairments, as well as their potential as pharmacological targets. Overall, the evidence discussed supports a broader conceptualization of endocannabinoid and paracannabinoid signaling as pivotal regulators of natural rewards and opens new avenues for the development of targeted interventions for motivational and reward-related disorders.
诸如食物、交配和社交互动等自然奖励对于生存和物种繁衍至关重要，其调节涉及动机、认知和情感过程的复杂相互作用。在过去二十年中，内源性大麻素系统及其类大麻素对应物作为这些行为的关键调节因子受到了越来越多的关注。本综述旨在全面概述内源性大麻素和类大麻素系统在调节自然奖励驱动行为中所起的作用，重点关注进食、生殖行为和社交互动。我们强调内源性大麻素系统——主要通过CB1受体信号传导——如何调节参与能量平衡、奖励处理和情绪调节的中枢和外周回路。同时，我们探讨类大麻素的作用，如油酰乙醇胺（OEA）、棕榈酰乙醇胺（PEA）和硬脂酰乙醇胺（SEA），它们主要通过非大麻素受体发挥作用，并有助于调节食欲、性动机和社会行为。特别关注这些系统在肥胖症、饮食失调、性功能障碍和社交障碍病理生理学中的相关性，以及它们作为药物靶点的潜力。总体而言，所讨论的证据支持将内源性大麻素和类大麻素信号传导更广泛地概念化为自然奖励的关键调节因子，并为开发针对动机和奖励相关障碍的靶向干预措施开辟了新途径。
