Attention-deficit/hyperactivity disorder (ADHD) a common neurodevelopmental disorder of childhood and often comorbid with other externalizing disorders (EDs). There is evidence that externalizing behaviors share a common genetic etiology. Recently, a genome-wide, multigenerational sample linked variants in the Lphn3 gene to ADHD and other externalizing behaviors. Likewise, limited research in animal models has provided converging evidence that Lphn3 plays a role in EDs. This study examined the impact of Lphn3 deletion (i.e., Lphn3^−/−) in rats on measures of behavioral control associated with externalizing behavior. Impulsivity was assessed for 30 days via a differential reinforcement of low rates (DRL) task and working memory evaluated for 25 days using a delayed spatial alternation (DSA) task. Data from both tasks were averaged into 5-day testing blocks. We analyzed overall performance, as well as response patterns in just the first and last blocks to assess acquisition and steady-state performance, respectively. “Positive control” measures on the same tasks were measured in an accepted animal model of ADHD–the spontaneously hypertensive rat (SHR). Compared with wildtype controls, Lphn3^−/− rats exhibited deficits on both the DRL and DSA tasks, indicative of deficits in impulsive action and working memory, respectively. These deficits were less severe than those in the SHRs, who were profoundly impaired on both tasks compared with their control strain, Wistar-Kyoto rats. The results provide evidence supporting a role for Lphn3 in modulating inhibitory control and working memory, and suggest additional research evaluating the role of Lphn3 in the manifestation of EDs more broadly is warranted.

中文翻译：

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两种不同注意力缺陷多动障碍大鼠模型的执行功能评估：自发性高血压与 Lphn3 基因敲除大鼠

注意缺陷/多动障碍 (ADHD) 是一种常见的儿童神经发育障碍，通常与其他外在障碍 (ED) 并存。有证据表明外化行为具有共同的遗传病因。最近，一个全基因组、多代样本将Lphn3基因的变异与 ADHD 和其他外化行为联系起来。同样，对动物模型的有限研究提供了Lphn3在 ED 中发挥作用的一致证据。本研究检查了Lphn3缺失的影响（即Lphn3 ^-/-) 在大鼠中与外化行为相关的行为控制措施。通过低速率 (DRL) 任务的差异强化评估 30 天的冲动性，并使用延迟空间交替 (DSA) 任务评估 25 天的工作记忆。来自这两项任务的数据被平均到 5 天的测试块中。我们分析了整体性能以及第一个和最后一个块中的响应模式，以分别评估采集和稳态性能。在公认的 ADHD 动物模型——自发性高血压大鼠 (SHR) 中测量了相同任务的“阳性对照”措施。与野生型对照相比，Lphn3 ^-/-大鼠在 DRL 和 DSA 任务上均表现出缺陷，分别表明冲动行为和工作记忆存在缺陷。这些缺陷没有 SHR 中的缺陷严重，SHR 与其对照品系 Wistar-Kyoto 大鼠相比，在这两项任务上都严重受损。结果提供了支持Lphn3在调节抑制控制和工作记忆中的作用的证据，并表明需要开展更多研究来更广泛地评估Lphn3在 ED 表现中的作用。