Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are chemogenetic tools commonly-used to manipulate brain activity. The most widely-used synthetic DREADD ligand, clozapine-N-oxide (CNO), is back-metabolized to clozapine which can itself activate endogenous receptors. Studies in non-DREADD-expressing rodents suggest CNO or a DREADD agonist that lacks active metabolites, such as Compound 21 (C21), change rodent behavior (e.g. decrease locomotion), but chronic injection of CNO does not change locomotion. However, it is unknown if chronic CNO changes behaviors relevant to locomotion, exploration, anxiety, and depression, or if chronic C21 changes any aspect of mouse behavior. Here non-DREADD-expressing mice received i.p. Vehicle (Veh), CNO, or C21 (1 mg/kg) 5 days/week for 16 weeks and behaviors were assessed over time. Veh, CNO, and C21 mice had similar weight gain over the 16-week-experiment. During the 3rd injection week, CNO and C21 mice explored more than Veh mice in a novel context and had more open field center entries; however, groups were similar in other measures of locomotion and anxiety. During the 14th-16th injection weeks, Veh, CNO, and C21 mice had similar locomotion and anxiety-like behaviors. We interpret these data as showing chronic Veh, CNO, and C21 injections given to male non-DREADD-expressing mice largely lack behavioral effects. These data may be helpful for behavioral neuroscientists when study design requires repeated injection of these DREADD agonists.

由设计药物（DREADDs）独家激活的设计受体是通常用于操纵大脑活动的化学生成工具。最广泛使用的合成DREADD配体氯氮平-N-氧化物（CNO）被逆代谢为氯氮平，氯氮平本身可以激活内源性受体。对未表达DREADD的啮齿动物的研究表明，CNO或缺乏活性代谢产物（例如化合物21（C21））的DREADD激动剂会改变啮齿动物的行为（例如，降低运动能力），但长期注射CNO不会改变运动能力。但是，尚不清楚慢性CNO是否改变与运动，探查，焦虑和抑郁有关的行为，或者慢性C21是否改变小鼠行为的任何方面。在这里，未表达DREADD的小鼠每周5天接受ip媒介物（Veh），CNO或C21（1 mg / kg），共16周，并随时间评估其行为。薇，CNO，在16周的实验中，C21和C21小鼠的体重增加相似。在注射的第3周中，CNO和C21小鼠在新颖的背景下比Veh小鼠进行了更多探索，并且有更多的空地中心条目；但是，在其他运动和焦虑量度上，组别相似。在第14-16周的注射周中，Veh，CNO和C21小鼠具有相似的运动和焦虑样行为。我们将这些数据解释为显示，对不表达DREADD的雄性小鼠进行慢性Veh，CNO和C21注射在很大程度上缺乏行为影响。当研究设计要求重复注射这些DREADD激动剂时，这些数据可能对行为神经科学家有用。但是，在其他运动和焦虑量度上，组别相似。在第14-16周的注射周中，Veh，CNO和C21小鼠具有相似的运动和焦虑样行为。我们将这些数据解释为显示，对不表达DREADD的雄性小鼠进行慢性Veh，CNO和C21注射在很大程度上缺乏行为影响。当研究设计要求重复注射这些DREADD激动剂时，这些数据可能对行为神经科学家有用。但是，在其他运动和焦虑量度上，组别相似。在第14-16周的注射周中，Veh，CNO和C21小鼠具有相似的运动和焦虑样行为。我们将这些数据解释为显示，对不表达DREADD的雄性小鼠进行慢性Veh，CNO和C21注射在很大程度上缺乏行为影响。当研究设计要求重复注射这些DREADD激动剂时，这些数据可能对行为神经科学家有用。