Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats.

The prefrontal cortices in rats participate in a range of cognitive, emotional, and locomotor functions that are dependent on its rich catecholamine innervation. Sex differences identified in many of these functions suggest that the prefrontal cortex is also influenced by gonadal hormones. Previous studies have shown that prefrontal catecholamines can be modified by changes in the hormone environment in developing animals. The present analyses, carried out in male rats gonadectomized as adults, with and without supplementation with testosterone proprionate, and examined at intervals from two days to 10 weeks after surgery, revealed that both the anatomical organization of prefrontal catecholamine afferents, and a behavioral measure sensitive to their selective lesioning remain highly responsive to changes in testicular hormones in adulthood. Thus, gonadectomy in adult male rats rapidly led to a large but transient decrease in the density of tyrosine hydroxylase immunoreactivity in all layers of the dorsal anterior cingulate cortex. This was followed by a sustained period in which immunoreactivity in the supragranular layers returned to levels that were just below normal (between 72 and 79% of normal), and labeling in deep laminae stabilized at considerably elevated innervation densities (approximately 150% of normal). Neither the acute decrease nor the chronic over-innervation characteristic of gonadectomized animals was observed in rats that were gonadectomized and supplemented with testosterone proprionate. Open field activity assessed along a corresponding 10 week timeline showed that gonadectomized animals were significantly less active than hormonally intact controls, a behavioral pattern opposite to the hyperactivity which persists following prefrontal dopamine lesions. Gonadectomized animals supplemented with testosterone proprionate, on the other hand, had open field scores that were not significantly different from controls. Taken together, these findings indicate that the adult hormone environment provides a significant, and seemingly functionally significant influence over the catecholamine innervation of the rat prefrontal cortex. Such lifelong responsiveness of the prefrontal cortical catecholamines to circulating hormones suggests that gonadal steroids are an active component of the biology of normal adult cognition, and may also have relevance for cortical dysfunction in disorders such as schizophrenia which are not only strongly tied to the catecholamines, but exhibit considerable biases among men and women as well.