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

The spontaneously hypertensive rat (SHR) has been used as an animal model o f attention deficit hyperactivity disorder (ADHD). The present study was de signed to determine whether exposure to elevated androgen levels early in d evelopment demonstrated impairments in cognitive functioning, neuroendocrin e control, and brain development parallel to those seen in ADHD children. T he animals (SHR and Wistar (WKY) controls) were implanted with testosterone on postnatal day 10 and tested for behavior in a spatial cognition paradig m on postnatal day 45. Plasma samples were collected for determination of a drenocorticotrophin 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 o f catecholamine innervation) in the frontal cortex was compared between ani mals. The current data show that early testosterone treatment in SHR animal s resulted in additional deficits in spatial memory in the water maze, but was ineffective in altering the response of WKY animals. Furthermore, SHR r ats had high basal ACTH and low corticosterone levels that may indicate a d ysfunctional stress axis similar to other reports in humans with persistent ADHD. Finally, there was a further suppression of tyrosine hydroxylase-imm unoreactivity in the frontal cortex of androgen-treated SHR rats. These res ults support the hypothesis that early androgen treatment may support the n eurobiology of animals with genetic predisposition to hyperactivity, impuls ivity and inattention in a manner consistent with the enhanced expression o f ADHD-like behaviors. (C) 2000 Elsevier Science B.V. All rights reserved.