Effects of acute morphine pretreatment on the rate-decreasing and antagonist activity of naloxone

Rats responded under a schedule in which every 30th lever press (fixed ratio 30) produced a food pellet during sessions divided into six 5-min ratio components separated by 10-min timeout (TO) periods. Cumulative doses of morphine or naloxone were administered at the start of consecutive TO periods. When given alone, morphine decreased response rates in a dose-dependent manner, abolishing responding at 10 or 17.8 mg/kg. Naloxone doses of 0.1 and 1.0 mg/kg restored rates and patterns of behavior suppressed by a dose of 17.8 mg/kg morphine; doses of 0.32 to 10 mg/kg prevented the rate-decreasing effects of cumulative morphine doses. When administered alone, naloxone initially decreased response rates at a cumulative dose of 32 to 100 mg/kg; with repeated testing and intervening morphine exposure, the required cumulative dose was decreased to 10 or 32 mg/kg. An acute 10 mg/kg morphine pretreatment, given 4 h before the session, decreased the cumulative naloxone dose required to suppress rates an additional 10- to 30-fold. This effect was time-dependent and dose-dependent, and the usual naloxone dose-response function could be recaptured 1 week after the pretreatment effect was obtained. In contrast, acute morphine pretreatment did not alter either the cumulative dose of morphine itself required to suppress rates or the naloxone dose required to reverse or prevent morphine's rate-decreasing effects.