Abuse liability of the anesthetic propofol: self-administration of propofol in rats under fixed-ratio schedules of drug delivery

Rationale: Previous reports suggest that propofol (PPF) may have abuse pote ntial in humans. Hence, we hypothesized that PPF could reinforce self-admin istration behavior in other species. Positive reinforcing effects of PPF co uld be interpreted as an index of abuse liability. Objective: Acquisition a nd maintenance of i.v. PPF self-administration were examined in 12 rats. Me thods: 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 wer e initially given access to PPF (1.7 mg/kg per infusion). Once stable respo nding was established, various doses of PPF (0.56, 1.0, and 1.7 mg/kg per i nfusion) and vehicle (Intralipid 20%) were made available. Results: The num ber 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 rat s, 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 d ecreased the number of vehicle infusions per session in these rats, while P PF maintained a higher number of infusions than vehicle under this FR value in six of seven rats. Conclusion: 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.