Me. Coussonsread et al., PAVLOVIAN CONDITIONING OF MORPHINE-INDUCED ALTERATIONS OF IMMUNE STATUS - EVIDENCE FOR OPIOID RECEPTOR INVOLVEMENT, Journal of neuroimmunology, 55(2), 1994, pp. 135-142
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.