Behavioral and Neuroanatomical Investigation of Attention Deficit Hyperactivity Disorder Pathogenesis in Juvenile Spontaneously Hypertensive Rats

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders of childhood, characterized by locomotor hyperactivity, impaired sustained attention, impulsivity, and distractibility. Recently, the dysfunction of different synaptic circuits in the prefrontal cortex (PFC) has been shown. Previous studies have attributed the pathophysiological mechanism of ADHD to disturbances in the dopaminergic system. In this study, we tested the hypothesis that spontaneously hypertensive rats (SHR), which are considered a validated animal model of ADHD, have altered dopaminergic innervation and increased locomotor activity. Here, we performed immunohistochemical tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) staining. The mesocortical dopaminergic system appears to be normal in juvenile SHR, as suggested by (i) no alteration in the area density of TH-immunoreactive (TH-ir) dopaminergic neurons in the VTA, (ii) no alterations in the volume density of TH-ir fibers in layer I of the PrL subregion of mPFC, (iii) no alteration in the percentage of TH-ir dopaminergic fibers in layer I of the PrL subregion of mPFC as revealed by TH and/or DBH immunoreactivity. Furthermore, the SHR showed increased locomotor activity than WKY in the open field test. The demonstration of no alteration in mesocortical dopaminergic neurons and fiber in SHR raises some concern about the position of SHR as an animal model of the inattentive subtype of ADHD. However, these results strengthen this strain as an animal model of hyperactive/impulsive subtype ADHD for future studies that may elucidate the underlying mechanism mediating hyperactivity and test various treatment strategies.