Uncoupling of receptors is essential for opiate-induced desensitization (tolerance) in neuroblastoma x glioma hybrid cells NG 108-15.

Neuroblastoma x glioma hybrid cells NG 108-15 were chronically treated with opioid agonists and tested for their development of "tolerance" as evaluated by the loss of inhibitory activity of opioids upon cAMP-accumulation. Desensitization was dose-dependent and non-competitive and highly selective, since the activity of other, non-opioid inhibitory compounds, such as noradrenaline and carbachol, was not altered. Moreover, naloxone-induced "withdrawal signs" (revealed in the lack of change in cAMP) were lacking in preparations completely desensitized ("tolerant") towards opiate effects. These results reject the assumption of a common biochemical mechanism underlying both opiate tolerance and dependence and rather support the significance of an uncoupling of receptors from subsequent effector systems upon chronic opiate action.