Lysle D T, Luecken L J, Maslonek K A
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
Brain Behav Immun. 1992 Jun;6(2):179-88. doi: 10.1016/0889-1591(92)90017-i.
Recent research has shown that presentations of an unconditioned aversive stimulus, such as electric shock, can induce alterations of immune function in rats. Furthermore, it has been demonstrated that an innocuous stimulus paired with an unconditioned aversive stimulus can acquire immunomodulatory properties. Research has suggested that endogenous opioid activity is responsible for the alterations of immune function by unconditioned aversive stimulation. The present study evaluated the effect of administration of opiate receptor antagonists, naltrexone and N-methylnaltrexone, on the immunomodulatory effect of a conditioned stimulus (CS) that had been paired with electric footshock. Naltrexone dose-dependently attenuated the CS-induced suppression of the in vitro proliferative response of splenic lymphocytes to concanavalin A, lipopolysaccharide, and a combination of ionomycin and phorbol myristate acetate. Naltrexone also attenuated the CS-induced reduction in natural-killer cell activity. In contrast, the quaternary form of naltrexone, N-methylnaltrexone, did not significantly attenuate the CS-induced immunomodulatory effects. Collectively, these findings indicate that endogenous opioid activity is involved in CS-induced alterations of immune function. Moreover, the lack of effectiveness of N-methylnaltrexone in attenuating the CS-induced immunomodulatory effect suggests that the opioid receptors involved in the effect are located in the central nervous system.
最近的研究表明，呈现无条件厌恶刺激，如电击，可诱导大鼠免疫功能改变。此外，已证明与无条件厌恶刺激配对的无害刺激可获得免疫调节特性。研究表明，内源性阿片类活性是无条件厌恶刺激导致免疫功能改变的原因。本研究评估了阿片受体拮抗剂纳曲酮和N-甲基纳曲酮给药对与足部电击配对的条件刺激（CS）免疫调节作用的影响。纳曲酮剂量依赖性地减弱了CS诱导的脾淋巴细胞对刀豆球蛋白A、脂多糖以及离子霉素和佛波酯联合刺激的体外增殖反应的抑制。纳曲酮还减弱了CS诱导的自然杀伤细胞活性的降低。相比之下，纳曲酮的季铵形式N-甲基纳曲酮并未显著减弱CS诱导的免疫调节作用。总体而言，这些发现表明内源性阿片类活性参与了CS诱导的免疫功能改变。此外，N-甲基纳曲酮在减弱CS诱导的免疫调节作用方面无效，这表明参与该作用的阿片受体位于中枢神经系统。
