Cysteamine and naloxone attenuate aspartic acid-induced depression of ventilation

Aspartic acid (580 mg/kg, SC) causes a long-lasting depression of ventilation in adult male, but not female rats. The purpose of these experiments was to determine if the aspartic acid-induced depression of ventilation in awake male Sprague-Dawley rats is a consequence of the release of endogenous opioids or somatostatin. These neuromodulators have been shown to cause depression of ventilation. Pretreatment of male rats with the opioid antagonist naloxone (5 mg/kg) 10 min prior to aspartic acid attenuated the drop of ventilation from -138.6 +/- 26.9 ml/min to -63.4 +/- 16.6 ml/min (p < 0.01) by affecting both tidal volume and frequency of breathing. Naloxone administered prior to saline had no effect on ventilation. In another experiment, cysteamine (100 mg/kg), a somatostatin depleter, injected SC 2 h before aspartic acid administration also attenuated depression of ventilation by affecting frequency of breathing. Cysteamine alone, compared to saline, had no effect on ventilation over 24 h. These results suggest that aspartic acid acts by releasing endogenous opioids and somatostatin.