The effect of tolerance on opiate dependence as measured by the adenylate cyclase rebound response to naloxone in the NG108-15 model system.

The naloxone-induced adenylate cyclase rebound response produced by opiates in the NG108-15 cells is quite apparent after 48 h treatment with M but it is undetectable after incubation with the high intrinsic activity agonist etorphine. Replacement of agonists by antagonists in receptors that have been rendered inactive by tolerance does not elicit the AC rebound response, which is considered a biochemical correlate of dependence. This indicates that marked tolerance and receptor down-regulation induced by prolonged treatment with high efficacy agonists may reduce the level of dependence.