The ventilatory effects of cocaine in naive and methadone-treated rats

The ventilatory effects of acute exposure to cocaine, and acute exposure to cocaine and methadone, were determined by evaluating arterial blood PCO₂, PO₂, and pH in naive animals. Male Sprague-Dawley rats were treated (s.c.) acutely with 50, 100, or 150 mg/kg of cocaine or with 50 or 150 mg/kg of cocaine and 5 mg/kg of dl-methadone hydrochloride (i.p.); appropriate saline and 5 mg/kg methadone controls were used. The dosages of cocaine used represented 20 to 60% of the LD₅₀ for rats (250 mg/kg, s.c.). Blood was sampled from the tail artery before injection and 15, 30, 60, 120, 180, and 240 min postinjection. Animals exposed to cocaine acutely exhibited a slight ventilatory increase with a decrease in arterial PCO₂. Rats receiving acute methadone showed ventilatory depression with a decrease in PO₂, an increase in PCO₂ and a decrease in pH. With the exception of an ameliorating effect on PCO₂ changes in rats given 150 mg/kg of cocaine with methadone, acute exposure to cocaine and methadone did not alter arterial blood gases or pH. this study demonstrates that cocaine causes only mild stimulation on ventilation when given acutely to rats, and has little effect on the ventilatory depression caused by methadone.