Systemic administration of propentofylline does not attenuate morphine tolerance in non-injured rodents

Propentofylline is a phosphodiesterase inhibitor that has been shown to attenuate the onset of morphine tolerance when administered intrathecally to rats. The present studies examined whether systemic administration could be effective in attenuating morphine tolerance in non-injured rodents using a similar dosing paradigm. Propentofylline at 10, 30, or 50 mg/kg, administered intraperitoneally once daily for 5 days, was unable to attenuate morphine tolerance established by twice daily administration of 10 mg/kg morphine. These results suggest that direct delivery of propentofylline to the central nervous system (CNS) may be required in order to attenuate morphine tolerance.