Genetic correlates of morphine withdrawal in 14 inbred mouse strains.

Abstract

Male mice from 14 standard inbred strains were exposed to morphine in a sustained released preparation injected subcutaneously. Five hours later withdrawal was precipitated by intraperitoneal injection of naloxone. Mice were tested from 0 to 15 min after naloxone for withdrawal jumping behavior, and then from minute 15-16 for other signs, including boli count, presence of soft stool, lacrimation, "wet dog" shakes, and air chewing. They were also assessed for change in body temperature 17 min after naloxone. Strains differed markedly in the severity of withdrawal for jumping, change in body temperature, and number of fecal boli. Strains also differed in percentage of animals displaying soft stool and air chewing behavior. The other two signs were seen at too low frequency for analysis. Correlations of strain mean withdrawal severity with other responses to morphine and other abused drugs showed that high morphine withdrawal jumping and low change in body temperature were both genetically related to high morphine consumption, but not generally to other measures of morphine withdrawal or morphine sensitivity.