Naloxone microinjected into the arcuate nucleus has differential effects on ventilation in male and female rats

The arcuate nucleus of the hypothalamus, a highly sexually dimorphic brain region, has been called the bed nucleus for endogenous opioids. The potential contribution of opioids in this nucleus to modulate control of ventilation in male and female rats has not been investigated. The purpose of the present study is to determine the effect of microinjecting naloxone, an opioid receptor antagonist, into the arcuate nucleus of awake male and female rats on ventilation, oxygen consumption, heart rate, and blood pressure. Results of this study demonstrate that naloxone at doses of 1.5 and 3.0 nmol relative to vehicle caused a depression of ventilation due to a decrease of both frequency of breathing and tidal volume in male rats and a decreased response to a hypercapnic challenge in female rats. Although there were gender differences noted in oxygen consumption, heart rate, blood pressure, and ventilatory response to a hypoxic challenge, only oxygen consumption was significantly affected by naloxone. Potential mechanisms whereby naloxone may act to depressing ventilation are discussed.