OPIOID PHYSICAL-DEPENDENCE DEVELOPMENT - EFFECTS OF SINGLE VERSUS REPEATED MORPHINE PRETREATMENTS AND OF SUBJECTS OPIOID EXPOSURE HISTORY

In acute dependence, signs and symptoms of opioid withdrawal are preci pitated when an opioid antagonist (naloxone) is administered following acute (e.g. single dose) pretreatment with a mu agonist. This study e xamined the influence of amount of previous opioid exposure, both imme diate and remote, on intensity of precipitated withdrawal effects in a n acute dependence model. Two groups of subjects, opioid abusers (n = 20) and nonabusers (n = 20), received either one 15 mg/70 kg IM morphi ne pretreatment or two such pretreatments spaced 24 h apart. Naloxone challenge (30 mg/70 kg) followed 4.33 h after the second pretreatment. There were clear effects of morphine pretreatment condition (single v ersus repeated 15 mg) on the intensity of precipitated withdrawal resp onses elicited by naloxone. More intense effects were seen after the r epeated pretreatment, suggesting that physical dependence escalates wi th repeated opioid exposures spaced at appropriate intervals. Subjects with an opioid abuse history reported greater liking of agonist drug effects than did nonabusers, whereas nonabusers reported more sedating effects. However, an opioid abuse history did not influence the inten sity of precipitated withdrawal symptoms and signs. The latter finding suggests that a previous opioid exposure history does not dramaticall y modulate initial stages of physical dependence development during su bsequent opioid exposure episodes.