Pavlovian conditioning of morphine-induced alterations of immune status.

The present study provides the first demonstration that alterations of immune status can be conditioned to environmental stimuli paired with morphine administration. In the first manipulation, male Lewis rats received 0, 2, 4, 8 or 16 conditioning sessions during which a subcutaneous injection of morphine (15 mg/kg) was paired with a distinctive environment. The results showed that subsequent re-exposure to the distinctive environment induced a decrease in the mitogenic responsiveness of splenic lymphocytes and a decrease in natural killer cell activity in animals which had received 2, 4, 8 and 16 conditioning sessions. In the second manipulation, using two conditioning sessions, a wider range of immune measures was assessed and control groups were included to ascertain whether the observed immune alterations were due to Pavlovian conditioning processes. The results showed that the environment which had been paired with morphine altered the mitogenic responsiveness of blood and splenic lymphocytes, decreased natural killer cell activity and decreased interleukin-2 production. In contrast, the conditioned environment did not have any effect on mitogenic responsiveness of lymphocytes derived from the mesenteric lymph nodes. Data from the control groups revealed that the compartment-specific immune alterations were the result of a Pavlovian conditioning process.