Haloperidol is a typical antipsychotic drug commonly used to treat a broad range of psychiatric disorders related to dysregulations in the neurotransmitter dopamine (DA). DA modulates important physiologic functions and perturbations in Caenorhabditis elegans (C. elegans) and, its signaling have been associated with alterations in behavioral, molecular, and morphologic properties in C. elegans. Here, we evaluated the possible involvement of dopaminergic receptors in the onset of these alterations followed by haloperidol exposure. Haloperidol increased lifespan and decreased locomotor behavior (basal slowing response, BSR, and locomotion speed via forward speed) of the worms. Moreover, locomotion speed recovered to basal conditions upon haloperidol withdrawal. Haloperidol also decreased DA levels, but it did not alter neither dop-1, dop-2, and dop-3 gene expression, nor CEP dopaminergic neurons' morphology. These effects are likely due to haloperidol's antagonism of the D2-type DA receptor, dop-3. Furthermore, this antagonism appears to affect mechanistic pathways involved in the modulation and signaling of neurotransmitters such as octopamine, acetylcholine, and GABA, which may underlie at least in part haloperidol's effects. These pathways are conserved in vertebrates and have been implicated in a range of disorders. Our novel findings demonstrate that the dop-3 receptor plays an important role in the effects of haloperidol.

中文翻译：

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氟哌啶醇与秀丽隐杆线虫中 dop-3 受体的相互作用。

氟哌啶醇是一种典型的抗精神病药物，常用于治疗与神经递质多巴胺 (DA) 失调相关的多种精神疾病。DA 调节秀丽隐杆线虫（秀丽隐杆线虫）的重要生理功能和扰动，并且其信号传导与秀丽隐杆线虫的行为、分子和形态学特性的改变有关。在这里，我们评估了多巴胺能受体可能参与这些改变的发生，然后是氟哌啶醇暴露。氟哌啶醇延长了蠕虫的寿命并降低了它们的运动行为（基础减慢反应、BSR 和通过前进速度产生的运动速度）。此外，氟哌啶醇停药后，运动速度恢复到基础条件。氟哌啶醇也降低了 DA 水平，但它没有改变 dop-1、dop-2、和 dop-3 基因表达，也不是 CEP 多巴胺能神经元的形态。这些作用可能是由于氟哌啶醇对 D2 型 DA 受体 dop-3 的拮抗作用。此外，这种拮抗作用似乎影响了涉及神经递质（如章鱼胺、乙酰胆碱和 GABA）的调节和信号传导的机制途径，这可能至少部分是氟哌啶醇作用的基础。这些通路在脊椎动物中是保守的，并且与一系列疾病有关。我们的新发现表明 dop-3 受体在氟哌啶醇的作用中起着重要作用。这种拮抗作用似乎影响了涉及神经递质（如章鱼胺、乙酰胆碱和 GABA）的调节和信号传导的机制途径，这可能至少部分是氟哌啶醇作用的基础。这些通路在脊椎动物中是保守的，并且与一系列疾病有关。我们的新发现表明 dop-3 受体在氟哌啶醇的作用中起着重要作用。这种拮抗作用似乎影响了涉及神经递质（如章鱼胺、乙酰胆碱和 GABA）的调节和信号传导的机制途径，这可能至少部分是氟哌啶醇作用的基础。这些通路在脊椎动物中是保守的，并且与一系列疾病有关。我们的新发现表明 dop-3 受体在氟哌啶醇的作用中起着重要作用。