Gestational physical exercise prevents early-life behavioral impairments and normalizes dopamine D2 receptor expression in the frontal cortex in the offspring of a rat model of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity, and develops most frequently during childhood and adolescence. Spontaneously hypertensive rats (SHR) are the most used experimental model for the study of ADHD. SHR exhibit behavioral impairments that recapitulate phenotypes observed in individuals with ADHD. SHR further develop dopaminergic hypofunction in frontostriatal circuits and an imbalance in dopamine and norepinephrine systems. Maternal physical exercise (e.g., swimming) during pregnancy has been shown to promote angiogenesis, neurogenesis, learning, and memory in the offspring of control rats. We investigated the impact of gestational swimming on behavioral and dopaminergic parameters in childhood (1-2 weeks of age) and adolescent (4-5 weeks of age) SHR and Wistar Kyoto rats (WKY), used as a control. Maternal gestational swimming resulted in a reversal of neurodevelopmental impairments in behavior, assessed by the righting reflex and olfactory recognition tests, in the offspring. Furthermore, during adolescence, SHRs from exercised dams exhibited reduced novelty seeking, an important behavioral trait in this developmental period. Finally, SHRs exhibited increased expression of dopamine transporter (DAT) and D2 receptors (D2R) in the frontal cortex. D2R expression was normalized in the frontal cortex of adolescent SHRs whose mothers were exercised. Results suggest that physical exercise during pregnancy could be an effective preventative strategy against ADHD-associated behavioral and neurochemical phenotypes in the offspring. Graphical Abstract