Raony Ícaro, Domith Ivan, Lourenco Mychael V, Paes-de-Carvalho Roberto, Pandolfo Pablo
Laboratory of Neurobiology of Animal Behavior, Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói 24020-141, Brazil; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Laboratory of Cellular Neurobiology, Department of Neurobiology and Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói 24020-141, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jul 13;117:110555. doi: 10.1016/j.pnpbp.2022.110555. Epub 2022 Mar 26.
Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that has recently been implicated in several psychiatric conditions related to monoaminergic dysfunction, such as schizophrenia, substance use disorders, and mood disorders. Although attention-deficit/hyperactivity disorder (ADHD) is also related to changes in monoaminergic neurotransmission, studies that assess whether TAAR1 participates in the neurobiology of ADHD are lacking. We hypothesized that TAAR1 plays an important role in ADHD and might represent a potential therapeutic target. Here, we investigate if TAAR1 modulates behavioral phenotypes in Spontaneously Hypertensive Rats (SHR), the most validated animal model of ADHD, and Wistar Kyoto rats (WKY, used as a control strain). Our results showed that TAAR1 is downregulated in ADHD-related brain regions in SHR compared with WKY. While intracerebroventricular (i.c.v.) administration of the selective TAAR1 antagonist EPPTB impaired cognitive performance in SHR, i.c.v. administration of highly selective TAAR1 full agonist RO5256390 decreased motor hyperactivity, novelty-induced locomotion, and induced an anxiolytic-like behavior. Overall, our findings show that changes in TAAR1 levels/activity underlie behavior in SHR, suggesting that TAAR1 plays a role in the neurobiology of ADHD. Although additional confirmatory studies are required, TAAR1 might be a potential pharmacological target for individuals with this disorder.
痕量胺相关受体1（TAAR1）是一种G蛋白偶联受体，最近被认为与几种与单胺能功能障碍相关的精神疾病有关，如精神分裂症、物质使用障碍和情绪障碍。尽管注意力缺陷多动障碍（ADHD）也与单胺能神经传递的变化有关，但评估TAAR1是否参与ADHD神经生物学的研究却很缺乏。我们假设TAAR1在ADHD中起重要作用，可能是一个潜在的治疗靶点。在此，我们研究TAAR1是否调节自发性高血压大鼠（SHR，最有效的ADHD动物模型）和Wistar Kyoto大鼠（WKY，用作对照品系）的行为表型。我们的结果表明，与WKY相比，SHR中与ADHD相关的脑区TAAR1表达下调。虽然脑室内（i.c.v.）注射选择性TAAR1拮抗剂EPPTB会损害SHR的认知能力，但脑室内注射高度选择性TAAR1完全激动剂RO5256390可降低运动亢进、新奇诱导的运动，并诱导类似抗焦虑的行为。总体而言，我们的研究结果表明，TAAR1水平/活性的变化是SHR行为的基础，这表明TAAR1在ADHD的神经生物学中起作用。尽管还需要更多的验证性研究，但TAAR1可能是患有这种疾病的个体的潜在药理学靶点。
