Route of morphine administration modulates conditioned analgesic tolerance and hyperalgesia

The present experiments investigated the effects of route of drug injection on two of the phenomena associated with repeated, cued, morphine administration. Experiment 1 examined the degree of situational specificity of analgesic tolerance following 5 days of morphine (5 mg/kg) delivered either subcutaneously (SC) or intravenously (i.v.). Situationally specific tolerance was only observed following i.v. morphine, although nonspecific tolerance was evident in both instances. Experiment 2 indicated that this difference was not due to dose, as neither 2.5 or 7.5 mg/kg SC morphine produced demonstrable situationally specific tolerance. Experiment 3 examined the putative existence of compensatory responses underlying the observed tolerance. Hyperalgesia in response to the environment in which morphine was experienced was evident in animals trained with i.v. morphine, but not in those receiving repeated SC injections. Potential explanations for these effects of route of administration are discussed.