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

Propofol is a widely used intravenous anesthetic that can directly activate and positively modulate the GABA(A)-receptor. Propofol is not currently regulated under the USA Controlled Substances Act. The present study evaluated the intravenous reinforcing effects of propofol compared to the intravenous barbiturate anesthetic methohexital in baboons using a procedure in which doses of the test drug were substituted for a standard cocaine dose. Drug or vehicle was available for self-injection during daily 5.5-h sessions under a fixed-ratio 120 or 160 schedule of reinforcement. A 40-min timeout after 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 mg/kg/injection) and vehicle was characterized first. Cocaine maintained self-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 cocaine for at least 10 sessions. Propofol and methohexital maintained self-injection 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 alter food intake systematically. Propofol maintained peak mean levels of self-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 propofol self-injection in two baboons, and was decreased in the third baboon. These data indicate that propofol, like methohexital, can function as a positive reinforcer.