Early androgen treatment decreases cognitive function and catecholamine innervation in an animal model of ADHD

Abstract

The spontaneously hypertensive rat (SHR) has been used as an animal model of attention deficit hyperactivity disorder (ADHD). The present study was designed to determine whether exposure to elevated androgen levels early in development demonstrated impairments in cognitive functioning, neuroendocrine control, and brain development parallel to those seen in ADHD children. The animals (SHR and Wistar (WKY) controls) were implanted with testosterone on postnatal day 10 and tested for behavior in a spatial cognition paradigm on postnatal day 45. Plasma samples were collected for determination of adrenocorticotrophin hormone (ACTH) and corticosterone levels as indicators of the basal tone of the pituitary-adrenal neuroendocrine axis. In addition, the density of tyrosine hydroxylase-immunoreactive fibers (an indicator of catecholamine innervation) in the frontal cortex was compared between animals. The current data show that early testosterone treatment in SHR animals resulted in additional deficits in spatial memory in the water maze, but was ineffective in altering the response of WKY animals. Furthermore, SHR rats had high basal ACTH and low corticosterone levels that may indicate a dysfunctional stress axis similar to other reports in humans with persistent ADHD. Finally, there was a further suppression of tyrosine hydroxylase-immunoreactivity in the frontal cortex of androgen-treated SHR rats. These results support the hypothesis that early androgen treatment may support the neurobiology of animals with genetic predisposition to hyperactivity, impulsivity and inattention in a manner consistent with the enhanced expression of ADHD-like behaviors.