Nitrous oxide induces feeding in the nondeprived rat that is antagonized by naltrexone

Three experiments investigated a possible effect of nitrous oxide (N2O) on food intake in nondeprived male hooded rats in independent groups designs. Experiment 1 demonstrated a concentration-related increase in intake with increasing level of nitrous oxide (10-40% N2O), reaching statistical significance at 20% N2O when compared to room air controls (p < 0.05). In experiment 2, pretreatment with 10 and 20 mg/kg of the benzodiazepine antagonist, flumazenil, failed to significantly attenuate 30% N2O-induced hyperphagia. In Experiment 3, pretreatment with the opioid antagonist, naltrexone, effectively antagonized 30% N2O-induced hyperphagia. Pronounced attenuation (to 59% of 30% N2O-induced intake level over a 1 h period) at the lowest dose of naltrexone (0.1 mg/kg, p < 0.01) compared to vehicle level resulted in a shallow dose-response curve across the dose range tested (0.1-10.0 mg/kg). These results suggest that an endogenous opioid mechanism is prominently involved in the N2O-induced ingestive response.