In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of naloxone-precipitated opiate withdrawal in rats. It has been suggested that some behavioral indices of withdrawal may be more sensitive to precipitation by naloxone than some somatic signs of withdrawal. The purpose of the present study was to permit a quantitative assessment of the relative sensitivity to naloxone of a variety of behavioral and somatic indices of opiate withdrawal. Male Wistar rats were implanted sc with either two morphine(each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response functions were determined with 5everal 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 behavioral effects: 1) a reduction in spontaneous locomotor activity, 2) a disruption of schedule-controlled(fixed ratio 15) operant re-sponding 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 nonde-pendent(placebo pellet-implanted) rats. The EDso values for naloxone precipitation of all behavioral signs of withdrawal were below 0.013 mg/kg; the EDso values for naloxone precip-itation of most somatic withdrawal signs were higher. The be-havioral measures used in these studies therefore represent highly sensitive indices of opiate withdrawal.

Many models ofdrug addiction include, as key components, the development of dependence with chronic drug use and the emergence of withdrawal symptoms on abstinence. The withdrawal syndrome in humans is characterized by a number of overt, measurable somatic signs and symptoms(Jaffe, 1990) and a number ofaffective symptoms, including feelings of anxiety, restlessness, tension, hyperirritabifity and depression or dysphoria(Haertzen and Hooks, 1969; Henningfield et al., 1987; Jaffe, 1990). Clinical evidence indicates that the affective signs of opiate abstinence may be more relevant to drug craving and relapse to compulsive drug use than the somatic signs of withdrawal(Henningfield et at., 1987; Jas-inski et a!., 1985). Thus, animal models of the affective aspects of opiate withdrawal are important tools for under-standing the neurobiological basis of opiate dependence and for developing effective treatment strategies to facilitate