Quintanilha Thalia M, Costa Pietra M, Cardoso Ana L S, Battú Gabrieli S, Bastos Leonardo M, Dos Santos Bruno P, Müller Talise E, de Oliveira Tiago F, Piato Angelo, Kalueff Allan V, de Abreu Murilo S
Graduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil.
Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil.
J Neurochem. 2025 Jun;169(6):e70116. doi: 10.1111/jnc.70116.
Trace amines are biologically active compounds endogenously synthesized in the brain in small amounts and structurally resembling biogenic amines. Acting via specific trace amine-associated receptors (TAARs), they induce robust behavioral and physiological effects in humans and animals. However, although TAAR ligands have recently been suggested as novel putative anxiolytics, their central effects and evolutionary conservation of activity remain poorly understood. Here, we evaluated the acute effects of four major trace amines (beta-phenylethylamine, tryptamine, tyramine, and octopamine) on zebrafish anxiety-like and social (shoaling) behavior, as well as neurochemical and neuroendocrine (cortisol) responses. Beta-phenylethylamine, at a low concentration (12 μg/L), caused overt anxiolytic-like effects and reduced brain acetylcholine levels; at a high concentration (1000 μg/L) increased zebrafish anxiety-like behavior and whole-body cortisol levels. Acute tryptamine exposure (7 mg/L) evoked an anxiogenic-like effect, reduced shoaling and social interaction, and elevated brain acetylcholine and whole-body cortisol. Acute exposure to tyramine (15 μg/L) and octopamine (125, 500, and 1500 μg/L) induced similar anxiogenic-like effects, accompanied by increased whole-body cortisol without altering brain acetylcholine levels. Collectively, these findings not only emphasize the important role of trace amines in brain and behavior but support the growing complexity of their CNS effects in vivo across taxa and highlight the relevance of zebrafish models for drug screening based on targeting brain TAARs.
痕量胺是在大脑中内源性少量合成的生物活性化合物，其结构类似于生物胺。它们通过特定的痕量胺相关受体（TAARs）发挥作用，在人类和动物中诱导强烈的行为和生理效应。然而，尽管最近有人提出TAAR配体是新型的潜在抗焦虑药，但其中枢效应和活性的进化保守性仍知之甚少。在这里，我们评估了四种主要痕量胺（β-苯乙胺、色胺、酪胺和章鱼胺）对斑马鱼焦虑样和社交（群居）行为以及神经化学和神经内分泌（皮质醇）反应的急性影响。低浓度（12μg/L）的β-苯乙胺会产生明显的抗焦虑样效应并降低脑内乙酰胆碱水平；高浓度（1000μg/L）则会增加斑马鱼的焦虑样行为和全身皮质醇水平。急性暴露于色胺（7mg/L）会引发焦虑样效应，减少群居和社交互动，并提高脑内乙酰胆碱和全身皮质醇水平。急性暴露于酪胺（15μg/L）和章鱼胺（125、500和1500μg/L）会诱导类似的焦虑样效应，同时全身皮质醇增加，而不改变脑内乙酰胆碱水平。总的来说，这些发现不仅强调了痕量胺在大脑和行为中的重要作用，还支持了它们在体内跨物种的中枢神经系统效应日益复杂的观点，并突出了斑马鱼模型在基于靶向脑TAARs进行药物筛选方面的相关性。
