The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats.
The intracerebroventricular administration of the 17 amino acid peptide nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor (previously referred to as ORL-1 or OP4 receptor), reduces voluntary 10% ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Studies aimed at the pharmacological characterization of the receptor, which mediates the effect, have shown that the C-terminal 13 amino acid sequence is crucial for activity and that the selective NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)NH(2) blocks the effect of N/OFQ on ethanol drinking. In place conditioning studies, N/OFQ abolishes the conditioned place preference (CPP) induced by ethanol in msP rats, or by morphine in nonselected Wistar rats; these findings suggest that N/OFQ is able to abolish the rewarding properties of ethanol and morphine. Moreover, N/OFQ inhibits reinstatement of alcohol-seeking behavior induced to electric footshock stress, as well as reinstatement of alcohol-seeking behavior induced by ethanol-paired cues. Together, these findings suggest that N/OFQ and its receptor may represent an interesting target for pharmacological treatment of alcohol abuse.
Ciccocioppo
Roberto
R
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Via Scalzino 3, 62032 (MC), Camerino, Italy.
Economidou
Daina
D
Fedeli
Amalia
A
Massi
Maurizio
M
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D007276:Injections, Intraventricular; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology; D009042:Motivation; D018847:Opioid Peptides / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000187:drug effects / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology; D000094942:Nociceptin Receptor
D000427:Alcohol Deterrents; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; C466980:nociceptin orphanin FQ(1-17)OH; D000431:Ethanol; D009020:Morphine; D000094942:Nociceptin Receptor