title: Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice.
abstract: Like other endogenous enkephalinase inhibitors, human opiorphin peptide (QRFSR) attenuates catabolism of enkephalins and appears to be a promising therapeutic, displaying antinociceptive action in several pain models. However, its opioid-like side-effect profile is insufficiently characterized. In the present set of experiments, acute intraperitoneal administration of opiorphin produced an antinociceptive effect in the tail-flick test in mice (0.3mg/kg) and this action was inhibited by opioid receptor antagonist naloxone (3mg/kg). Repeated treatment with opiorphin changed the antinociceptive response neither to itself nor to morphine, suggesting the lack of tolerance and morphine cross-tolerance, respectively. Repeated treatment with opiorphin (3mg/kg) also failed to produce opioid dependence. Opiorphin (0.3 or 1mg/kg) produced no rewarding effects in the conditioned place preference test. However, at the dose of 3mg/kg, the peptide produced antidepressant-like effect in the forced swim test, and it did not affect locomotor activity. The present set of results confirms the beneficial effects of opiorphin in pain management, and suggests a lack of opioid-like side effects as well as the presence of antidepressant-like actions of this peptide.
authors.affiliation: Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow, Poland. nfpopik@cyf-kr.edu.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamysz
authors.forename: Joanna
authors.initials: J
authors.lastname: Kreczko
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Wróbel
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D003214:Conditioning, Classical / Q000502:physiology; D003863:Depression / Q000378:metabolism; D006801:Humans; D008124:Locomotion / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009483:Neuropsychological Tests; D009842:Oligopeptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D002491:Central Nervous System Agents; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D012471:Salivary Proteins and Peptides; C517879:glutaminyl-arginyl-phenylalanyl-seryl-arginine; D009270:Naloxone; D009020:Morphine