高剂量给予 DREADD 激动剂 JHU37160 可增加雄性大鼠的焦虑样行为。
High dose administration of DREADD agonist JHU37160 produces increases in anxiety-like behavior in male rats.
机构信息
Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA; Tulane University, New Orleans, LA 70118, USA.
Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
出版信息
Behav Brain Res. 2023 Aug 24;452:114553. doi: 10.1016/j.bbr.2023.114553. Epub 2023 Jun 21.
Designer receptors exclusively activated by designer drugs (DREADDs) are a promising tool for analyzing neural circuitry, and improved DREADD-selective ligands continue to be developed. Relative to clozapine-N-oxide (CNO), JHU37160 is a selective DREADD agonist recently shown to exhibit higher blood brain barrier penetrance and DREADD selectivity in vivo; however, relatively few studies have characterized the behavioral effects of systemic JHU37160 administration in animals. Here, we report a dose-dependent anxiogenic effect of systemic JHU37160 in male Wistar and Long-Evans rats, regardless of DREADD expression, with no impact on locomotor behavior. These results suggest that high dose (1 mg/kg) JHU37160 should be avoided when performing chemogenetic experiments designed to evaluate circuit manipulation on anxiety-like behavior in rats.
设计型受体仅被设计药物激活（DREADDs）是分析神经回路的一种有前途的工具，并且正在开发改进的 DREADD 选择性配体。与氯氮平-N-氧化物（CNO）相比，JHU37160 是一种最近显示出体内更高的血脑屏障通透性和 DREADD 选择性的选择性 DREADD 激动剂；然而，很少有研究描述过全身性 JHU37160 给药在动物中的行为影响。在这里，我们报告了全身性 JHU37160 在雄性 Wistar 和 Long-Evans 大鼠中具有剂量依赖性的焦虑作用，而与 DREADD 表达无关，对运动行为没有影响。这些结果表明，在进行化学遗传实验以评估对大鼠焦虑样行为的回路操作时，应避免使用高剂量（1mg/kg）JHU37160。
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