Open AccessAn assessment of executive function in two different rat models of attention‐deficit hyperactivity disorder: Spontaneously hypertensive versus Lphn3 knockout rats
Author(s) -
Sable Helen J. K.,
Lester Deranda B.,
Potter Joshua L.,
Nolen Hunter G.,
Cruthird Destinee M.,
Estes Lauren M.,
Johnson Alyssa D.,
Regan Samantha L.,
Williams Michael T.,
Vorhees Charles V.
Publication year - 2021
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12767
Subject(s) - impulsivity , working memory , attention deficit hyperactivity disorder , psychology , neurodevelopmental disorder , attention deficit , executive functions , spontaneously hypertensive rat , genetic model , animal model , cognition , developmental psychology , neuroscience , clinical psychology , medicine , gene , biology , genetics , blood pressure , autism
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.