Morphine-like discriminative stimulus effects of opioid peptides: possible modulatory role of D-Ala2-D-Leu5-enkephalin (DADL) and dynorphin A (1-13).
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 micrograms), depending upon ligand and animal, by morphine, by the mu-selective peptides DAGO[D-Ala2-NMePhe4-Gly(ol)-enkephalin] and FK33824[D-Ala2,NMePhe4-Met(O)5-(ol)-enkephalin], and by the delta-selective peptide, DADL[D-Ala2,D-Leu5)enkephalin]. The order of relative potency of these substances was: FK33824 greater than DAGO greater than morphine greater than DADL. In contrast, DPLPE[D-Pen2,L-Pen5)enkephalin], which has much greater delta receptor selectivity than does DADL, and dynorphin A(1-13) (0.1-10 micrograms), a kappa-receptor agonist, engendered choice responding appropriate for saline. When 1.0 micrograms 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 micrograms dynorphin A(1-13) and morphine attenuated the stimulus effects of morphine inconsistently. These results support previous findings that mu-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.
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004347:Drug Interactions; D004399:Dynorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D010446:Peptide Fragments; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C026843:dynorphin (1-13); D004399:Dynorphins; D009020:Morphine