Opioid dependence and cross-dependence in the isolated guinea-pig ileum.

The development of opioid dependence and tolerance attributed to selective types of opiate receptors was studied in the isolated ileum of guinea pigs chronically exposed to specific opioids. These investigations were based on reports that in this preparation highly tolerant opiate receptors may coexist with opiate receptors of almost unchanged sensitivity. Thus, the ilea were set up in vitro and tested for tolerance and dependence. Apparently precipitation of the withdrawal contracture, indicating dependence, proved a more sensitive parameter than the phenomenon of tolerance. Maximal dependence was determined at rather low degrees of tolerance (5 to 10 fold). The intensity of the withdrawal contracture failed to increase as opiate tolerance did. Furthermore, the experiments failed to present evidence for the existence of selective dependence at specific opiate receptor types. These findings may suggest multiple adaptational mechanisms upon chronic activation of opiate receptors. One mechanism may be responsible for the development of dependence and a low degree of tolerance, whilst a further increase of tolerance may be associated with changes at the opiate binding site level.