CHANGES IN OPIOID RECEPTOR DENSITY ON MURINE SPLENOCYTES INDUCED BY IN-VIVO TREATMENT WITH MORPHINE AND METHADONE

In a 24-hr time course study we reported previously that a single syst emic injection of morphine profoundly affected various immune paramete rs in mice. In the present study we examined whether these effects are mediated by changes in opioid receptor density on murine splenocytes after acute in vivo morphine (20 mg/kg s.c.) and methadone (12.5 mg/kg s.c.) at equianalgesic doses. To define the splenocyte subpopulations we used flow cytofluorimetric analysis with specific fluorescent mono clonal antibodies and calculated the binding of the fluoresceinyl opia te antagonist naloxone on opiate receptors. Both morphine and methadon e reduced the density of opiate receptors on B- and T-lymphocytes. Spe cifically, 20 min, 1 and 3 days after the injection there was a marked reduction (about 55%) in naloxone binding sites; these returned to ba se line after 5 days for T-lymphocytes and after 7 days for B-lymphocy tes. Despite the low proportion of macrophages among total splenocytes (about 10%), our results also indicate a tendency to a reduction in o piate receptor density also in the macrophage population. These findin gs indicate that a single exposure to morphine and methadone results i n a strong, lasting down-regulation of opiate binding sites in murine splenocytes, probably accounting for the immunomodulation induced by o piates.