A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats.

Rats were trained to press a lever (respond) under a fixed-ratio 20 schedule for food presentation. Administration of 10 or 25 mg of naloxone (NX) per kg i.p. to drug-naive rats supressed responding whereas 1 mg of NX per kg was without effect. However, administration of 0.25 mg of NX per kg to rats which had received 10 or 15 mg of morphine sulfate per kg 48 hours previously induced small, but statistically reliable, decrements in responding. Rats implanted with one pellet containing 75 mg of morphine base displayed tolerance to the depressant effects of the morphine pellet within 2 days after implantation. A systematic study of the effects of naloxone given to morphine tolerant-dependent rats revealed good concordance between the amount of weight lost and the severity of behavioral disruption, within the same subject, after administration of the antagonist. Although 0.03 mg of NX per kg given 3 to 6 days after pellet implantation significantly suppressed responding, 0.1 mg of NX per kg was required to produce a significant reduction in body weight. Semiweekly injections of 1 mg of NX per kg continued to suppress responding up to 4 weeks after implantation of a single morphine pellet. The body weight changes were significant only up to 3 weeks after implantation. The data suggest that disruption of fixed-ratio responding is a sensitive indicator of antagonist-precipitated morphine withdrawal.