Gonadectomy and Hormone Replacement Affects In Vivo Basal Extracellular Dopamine Levels in the Prefrontal Cortex but Not Motor Cortex of Adult Male Rats

Gonadectomy in adult male rats is known to impair performance on dopamine (DA)-dependent prefrontal cortical tasks and selectively dysregulate end points in the mesoprefrontal DA system including axon density. In this study, in vivo microdialysis and high-pressure liquid chromatography were used to determine whether short (4 day)- and/or long-term (28 day) gonadectomy and hormone replacement might also influence the more functionally relevant metric of basal extracellular DA level/tone. Assessments in medial prefrontal cortex revealed that DA levels were significantly lower than control in 4-day gonadectomized rats and similar to control in 4-day gonadectomized animals supplemented with both testosterone and estradiol. Among the long-term treatment groups, DA levels were significantly higher than control in gonadectomized rats and gonadectomized rats given estradiol but were similar to control in rats given testosterone. In contrast, extracellular DA levels measured in motor cortex were unaffected by long- or short-term gonadectomy. The effects of gonadectomy and hormone replacement on prefrontal cortical DA levels observed here parallel previously identified effects on prefrontal DA axon density and could represent hormone actions relevant to the modulation of DA-dependent prefrontal cortical function and perhaps its dysfunction in disorders such as schizophrenia, attention deficit hyperactivity disorder, and autism where males are disproportionately affected relative to females.