RELATIVE SENSITIVITY TO NALOXONE OF MULTIPLE INDEXES OF OPIATE WITHDRAWAL - A QUANTITATIVE DOSE-RESPONSE ANALYSIS

In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of na loxone-precipitated opiate withdrawal in rats. it has been suggested t hat some behavioral indices of withdrawal may be more sensitive to pre cipitation by naloxone than some somatic signs of withdrawal. The purp ose of the present study was to permit a quantitative assessment of th e relative sensitivity to naloxone of a variety of behavioral and soma tic indices of opiate withdrawal. Male Wistar rats were implanted s.c. with either two morphine (each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response func tions were determined with several behavioral paradigms and ratings of a variety of somatic withdrawal signs. in dependent rats, very low (0 .004 or 0.01 mg/kg) doses of naloxone produced the following behaviora l effects: 1) a reduction in spontaneous locomotor activity, 2) a disr uption of schedule-controlled (fixed ratio 15) operant responding for food, 3) an elevation in intracranial self-stimulation thresholds and 4) a conditioned place aversion. These same doses of naloxone produced no significant effects in nondependent (placebo pellet-implanted) rat s. The ED(50) values for naloxone precipitation of all behavioral sign s of withdrawal were below 0.013 mg/kg; the ED(50) values for naloxone precipitation of most somatic withdrawal signs were higher. The behav ioral measures used in these studies therefore represent highly sensit ive indices of opiate withdrawal.