Morphine-like discriminative stimulus effects of opioid peptides: possible modulatory role ofd-Ala2-d-Leu5-enkephalin (DADL) and dynorphin A(1-13)

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Abstract
The role of the different opioid receptors was studied in rats trained to discriminate SC injections of 3.0 mg/kg morphine from saline by tests for generalization to graded doses of morphine and receptor-selective peptides administered into the lateral cerebral ventricle. Dose-dependent morphine-like stimulus effects were produced over a wide range of doses (0.001–30 μg), depending upon ligand and animal, by morphine, by themu-selective peptides DAGO[d-Ala2-NMePhe4-Gly(ol)-enkephalin] and FK33824[d-Ala2,NMePhe4-Met(O)5-(ol)-enkephalin], and by thedelta-selective peptide, DADL[d-Ala2,d-Leu5enkephalin]. The order of relative potency of these substances was: FK33824>DAGO>morphine>DADL. In contrast, DPLPE[d-Pen2,l-Pen5)enkephalin], which has much greaterdelta receptor selectivity than does DADL, and dynorphin A(1-13) (0.1–10 μg), akappa-receptor agonist, engendered choice responding appropriate for saline. When 1.0 μg DADL, a dose lacking morphine-like discriminative effects, was administered concurrently with SC morphine, the stimulus effects of morphine were potentiated. Concurrent administration of 10 μg dynorphin A(1-13) and morphine attenuated the stimulus effects of morphine inconsistently. These results support previous findings thatmu-opioid receptors are of primary importance in mediating the morphine-like discriminative effects of opioid peptides. They also suggest that morphine-like discriminative effects can be modulated by other types of opioid receptors.