Adult Levels of Testosterone Alter Catecholamine Innervation in an Animal Model of Attention-Deficit Hyperactivity Disorder

Abstract

The spontaneously hypertensive rat (SHR) has been used as an animal model of attention-deficit hyperactivity disorder (ADHD). This disorder, which is most prevalent in males during childhood, persists in adulthood more frequently in females. Since other work has shown that neonatal testosterone levels may be a contributing factor in the expression of ADHD-like behavior, the present study was designed to determine whether androgen levels also altered the neurobiology of adult SHRs compared to Wistar (WKY) controls. Males castrated on postnatal day 45 were implanted with testosterone, and the density of tyrosine-hydroxylase-immunoreactive (TH-ir) fibers (an indicator of catecholamine innervation) in the frontal cortex was compared between animals. The data show that testosterone-treated SHRs were associated with higher levels of TH immunoreactivity in the frontal cortex and hippocampus than WKY rats. These results may explain why high circulating levels of testosterone during adulthood do not support an increase in ADHD-like behavior in both the animal model and human males.