Morphine-induced thymic hypoplasia is glucocorticoid-dependent

Mice administered morphine as a s.c. pellet implant exhibit a marked and sustained thymic hypoplasia as well as suppression of T lymphocyte functions. In the present study, the effects of morphine on thymocyte differentiation were characterized. Morphine produced a significant decrease in both the number and proportion of CD4+/CD8+ double positive (DP) cells. The percentage of the CD4+/CD8-, CD4-/CD8+, and CD4-/CD8- double negative subsets in these mice was proportionally increased. Morphine also increased the proportion of cells expressing either the epsilon-chain of the CD3 complex or the IL-2R. The initial reduction in the proportion of DP thymocytes appeared fully recovered by 10 days post-implantation, although the number of DP thymocytes gradually returned to normal over a 3-wk period. Morphine administration resulted in a marked increase in serum corticosterone levels, and a single injection of dexamethasone mimicked the effects of morphine on thymus differentiation. Furthermore, adrenalectomy abolished the morphine-induced decrease in CD4+/CD8+ thymocytes relative to a sham-operated group. The present findings are consistent with the hypothesis that morphine-induced thymic hypoplasia may be mediated by an increase in the circulating levels of corticosterone.