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.