Opioid dependence in the guinea-pig myenteric plexus is controlled by non-tolerant and tolerant opioid receptors

The experiments concerned the association of opioid dependence with specific opioid receptors. Previous investigations have demonstrated that tolerance may be confined to only one type of opioid receptor. These findings could suggest that dependence develops invariably only with receptors which have been rendered tolerant. We report here that in the guinea-pig isolated ileum, which has been made selectively tolerant to a μ-receptor agonist, naloxone may precipitate a sign of dependence at μ-receptors chronically activated and at naive κ-receptors. Furthermore, suppression of the withdrawal contracture in preparations rendered dependent on a μ-receptor agonist can be achieved by very low concentrations of a κ-agonist, e.g. dynorphin A. These findings challenge the current concept that confines drug dependence only to that opioid receptor type which has been activated chronically.