The effect of in vitro methadone administration on trophoblast tissue opioid receptors and mediated responses

Abstract

Summary Term placental villus tissue explant culture was shown to be a suitable model system for investigating the effect of chronic administration of methadone on opioid receptors binding sites and mediated responses. The viability of villus tissue in culture was determined over a period of six days by glucose utilization, hCG, and hPL release, LDH activity, and morphological examination by light microscopy. All parameters demonstrated that both non-treated and methadone treated tissue remained viable for the duration of culture. A loss of 80% of opioid binding sites was observed after one day of culture in methadone-treated and non-treated tissue. However, both tissues maintained their responsiveness to opioids. After two days of culture, a further but slight decrease in the number of opioid receptor binding sites was observed in both non-treated and treated tissue. At the same time, methadone-treated tissue lost its responsiveness to opioids, whereas non-treated tissue retained it. The observed decrease in the number of opioid binding sites could be due to either a decrease in affinity or in Bmax for the ligand used, or both. The presence of similar number of opioid binding sites in cultured tissues but with the loss of responsiveness after two days in treated tissue only suggests a shift in the concentration response curve to the right.