Inbred low anxiety-related behavior (LAB) mice – a mouse model of attention-deficit hyperactivity disorder (ADHD)?

ADHD is a complex neurobiological disorder characterized by inattention, hyperactivity, impulsivity and cognitive deficits. Pharmacological studies have revealed that the psychostimulants (e.g. amphetamine) increased general activity in adults, while exerting a calming effect in ADHD patients. CD1 mice selectively bred for low (LAB), normal (NAB) and high (HAB) levels of innate anxiety show strong difference in locomotion in the open field. Hence, hyperactive LAB mice were proposed as a genetic model for ADHD. We employed several behavioral tasks to evaluate basal and pharmacologically modulated levels of locomotion, attention and cognitive abilities in the three lines. In a holeboard task, in addition to increased locomotion, LAB mice showed decreased exploration of 16 holes, implying their inattention to the testing context. LAB mice were impaired in acquisition and relearning in a water cross-maze, indicating a deficit in egocentric and allocentric navigation as well as in behavioral flexibility. LAB mice also showed reduced social memory upon exploration of conspecifics. Amphetamine administration decreased locomotion, but failed to reverse the cognitive deficits in LAB mice. The data state that hyperactivity, attention deficit, impaired spatial learning and social memory attribute to LAB mice. The differential response to amphetamine in LAB versus HAB/NAB mice supports the hypothesis that LAB mice fulfill not only face but predictive validity of an animal model of ADHD.