PAVLOVIAN CONDITIONING OF MORPHINE-INDUCED ALTERATIONS OF IMMUNE STATUS - EVIDENCE FOR OPIOID RECEPTOR INVOLVEMENT

Prior work in our laboratory has shown that morphine's immunomodulator y effects can become conditioned to environmental stimuli that predict drug administration. These immune alterations include conditioned cha nges in natural killer cell activity, interleukin-2 production, and mi togen-induced lymphocyte proliferation. The present study examined the involvement of opioid receptor activity in the establishment and expr ession of conditioned morphine-induced alterations of immune status. D uring the training phase of the experiment, Lewis rats received two co nditioning sessions during which a subcutaneous injection of 15 mg/kg morphine sulfate was paired with exposure to a distinctive environment . On the test day, animals were re-exposed to the distinctive environm ent alone prior to sacrifice. Saline or naltrexone (0.3, 1.0, 3.0 or 1 0.0 mg/kg) was administered during either the training or the test ses sion. Administration of naltrexone prior to training antagonized the d evelopment of all of the conditioned alterations of immune status incl uding changes in the mitogenic responsiveness of splenocytes, suppress ion of natural killer cell activity, and interleukin-2 production by s plenocytes. Naltrexone administration prior to testing also was effect ive in antagonizing the expression of a subset of morphine-induced con ditioned alterations in immune status. Taken together, these studies i ndicate that opioid receptor activity is involved in the establishment of conditioned morphine-induced immune alterations, as well as in the expression of a subset of these conditioned alterations df immune sta tus.