Influence of nociceptin(1-17) fragments and its tyrosine-substituted derivative on morphine-withdrawal signs in rats.
Our previous studies demonstrated that endogenous ligand of nociceptin (NOP) receptor, nociceptin(1-17) (also known as orphanin FQ), inhibits morphine-withdrawal syndrome measured as wet dog shakes in rats [Life Sci. 66 (2000) PL119]. This peptide is metabolized in the spinal cord, both in vitro and in vivo, to shorter fragments, including nociceptin(1-11) and nociceptin(1-6). These fragments, formed after cleavage by endogenous peptidase, are behaviorally active and modulate nociception in a bi-phasic process [Peptides 20 (1999) 239]. As these peptides induced transient naloxone-reversible analgesia in behavioral tests [Peptides 20 (1999) 239], in the present study we tested the influence of nociceptin(1-11) (10 and 20 microg) and nociceptin(1-6) (10, 20 and 40 microg) on the morphine-withdrawal syndrome in rats. Furthermore, the modified fragment of nociceptin(1-6) with an opioid-message domain achieved by replacement of Phe1 with Tyr was tested. Morphine-withdrawal syndrome was precipitated by the i.p. injection of naloxone hydrochloride (2 mg/kg), 72 h after implantation of morphine pellets. The wet-dog shakes were chosen for statistical analyses of the abstinence signs. The results show that nociceptin(1-11) and (1-6) attenuate this morphine-withdrawal symptom. The replacement of Phe1 with Tyr in nociceptin(1-6) fragment did not potentiate the influence of nociceptin(1-6) on wet dog shakes precipitated by naloxone in morphine-dependent rats.
Department of Pharmacodynamics, Medical University, Staszica 4, 20-081 Lublin, Poland. jolka@panaceum.am.lublin.pl
Jolanta
J
Kotlinska
Tomasz
T
Dylag
Piotr
P
Rafalski
Sylwia
S
Talarek
Maria
M
Kosior
Jerzy
J
Silberring
D000818:Animals; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D014443:Tyrosine / Q000378:metabolism*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000097629:Nociceptin
D009020:Morphine; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D014443:Tyrosine; D014665:Vasodilator Agents; D000097629:Nociceptin; C121233:nociceptin (1-11)