Abstract

The dose-response relationships of naloxone to selected signs of the precipitated abstinence syndrome were studied in male rats rendered physically dependent on morphine by subcutaneous implantation of two morphine pellets. Abstinence behavior was precipitated by i.p. injection of naloxone hydrochloride 72 hours after the first pellet implant. The median effective dose of naloxone was determined for the quantal abstinence responses of diarrhea, abnormal posturing, ear blanching, ptosis, teeth chattering, swallowing movements, escape attempts and wet shakes. Other signs of precipitated abstinence such as the incidence of seminal emissions and chromodacryorrhea as well as the average number of wet shakes and escape attempts per responding animal were found to exhibit a poor dose-response relationship with increasing naloxone dosage in the tested range of 0.04 to 10 mg/kg. Loss of body weight, measured three hours after naloxone administrations, was correlated to the log dose of naloxone. The relative merits of different criteria for quantifying the morphine abstinence syndrome are discussed.