Comparison of the intravenous reinforcing effects of propofol and methohexital in baboons

Propofol is a widely used intravenous anesthetic: that can directly activat e and positively modulate the GABA(A)-receptor. Propofol is not currently r egulated under the USA Controlled Substances Act. The present study evaluat ed the intravenous reinforcing effects of propofol compared to the intraven ous barbiturate anesthetic methohexital in baboons using a procedure in whi ch doses of the test drug were substituted for a standard cocaine dose. Dru g or vehicle was available far self-injection during daily 5.5-h sessions u nder a fixed-ratio 120 or 160 schedule of reinforcement. A 40-min timeout a fter each injection limited the maximum of injections per session to eight. Food pellets were available continuously during the session under a fixed ratio 10 schedule of reinforcement. Self-injection of cocaine (0.001-0.32 m g/kg/injection) and vehicle was characterized first. Cocaine maintained sel f-injection in a dose-dependent manner, with peak injections maintained by 0.32 mg/kg. Vehicle and each dose of propofol (0.1-1.0 mg/kg/injection) and methohexital (0.01-1.0 mg/kg/injection) were substituted for 0.32 mg/kg co caine for at least 10 sessions. Propofol and methohexital maintained self-i njection greater than vehicle in all three baboons, and these effects were dose dependent. Methohexital maintained peak mean levels of self-injection that were > 6 injections/day at doses of 0.56 and 1.0 mg/kg, and did not al ter food intake systematically. Propofol maintained peak mean levels of sel f-injection at 1.0 mg/kg that ranged from 2.2 to > 6 injections/day across the baboons. Food intake was increased slightly above vehicle levels by pro pofol self-injection in two baboons, and was decreased in the third baboon. These data indicate that propofol, like methohexital, can function as a po sitive reinforcer. (C) 1999 Elsevier Science Ireland Ltd. All rights reserv ed.