Abuse liability of the anesthetic propofol: self-administration of propofol in rats under fixed-ratio schedules of drug delivery.
BACKGROUND
Previous reports suggest that propofol (PPF) may have abuse potential in humans. Hence, we hypothesized that PPF could reinforce self-administration behavior in other species. Positive reinforcing effects of PPF could be interpreted as an index of abuse liability.


OBJECTIVE
Acquisition and maintenance of i.v. PPF self-administration were examined in 12 rats.


METHODS
Six rats were initially given access to methohexital (MHX, 2.0 mg/kg per infusion) under a fixed ratio (FR) 1 schedule, while the other six were initially given access to PPF (1.7 mg/kg per infusion). Once stable responding was established, various doses of PPF (0.56, 1.0, and 1.7 mg/kg per infusion) and vehicle (Intralipid 20%) were made available.


RESULTS
The number of PPF infusions per session was an inverse function of dose, with 0.56 mg/kg and 1.0 mg/kg per infusion maintaining significantly more infusions per session than vehicle in most rats under the FR 1 schedule. For some rats, the number of vehicle infusions per session was equal to or greater than the number of PPF infusions. Increasing the response requirement to FR 5 decreased the number of vehicle infusions per session in these rats, while PPF maintained a higher number of infusions than vehicle under this FR value in six of seven rats.


CONCLUSIONS
PPF served as a reinforcer in rats under FR schedules of i.v. drug delivery, adding to the extant evidence that it has abuse potential.
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
M G
MG
LeSage
D
D
Stafford
J R
JR
Glowa
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008723:Methohexital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D019966:Substance-Related Disorders / Q000523:psychology*
D018686:Anesthetics, Intravenous; D008723:Methohexital; D015742:Propofol