Genetic strain differences in the opiate abstinence syndrome

Five strains of rats, two outbred (Sprague-Dawley and Holtzman) and three inbred strains (Buffalo, Lewis, and Fisher), received subcutaneous implants of either morphine or placebo pellets. The naloxone-precipitated opiate abstinence syndrome was observed after one, two, or three days of exposure to the implanted pellet. The presence or frequency of occurrence of fourteen abstinence signs was monitored both before and after a subcutaneous injection of naloxone hydrochloride (.4 mg/Kg). Inter-strain differences were present both pre- and post-naloxone injection in animals receiving either morphine or placebo. Differences were most evident in the frequency of occurrence of escape attempts, wet dog shakes, teeth chattering episodes, and activity counts. Following injection of naloxone, the profile of abstinence responses changed depending on the length of exposure to the implanted morphine pellet. This change was statistically significant in four of the strains observed; no significant effect of length of exposure was found in the response profile of Holtzman rats. For those strains showing a significant length-of-exposure effect, a discriminant function based on the abstinence syndrome profile was obtained. This function describes differences along the length-of-exposure dimension and may prove useful as a quantitative assessment of the abstinence syndrome.