Attenuation of ethanol self-administration and of conditioned reinstatement of alcohol-seeking behaviour by the antiopioid peptide nociceptin/orphanin FQ in alcohol-preferring rats.
BACKGROUND
Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor NOP, was shown to reduce home-cage ethanol consumption, ethanol-induced conditioned place preference and stress-induced reinstatement of alcohol-seeking behaviour.


OBJECTIVE
The present study, using genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, was designed to evaluate the effect of this opioid peptide on 10% ethanol and 10% sucrose self-administration, under a fixed-ratio 1 (FR 1) or a progressive-ratio (PR) schedule of reinforcement. Furthermore, using an experimental model of relapse in which rats were trained to lever press for ethanol in the presence of the discriminative stimulus of an orange odour (S(+)) and a 1-s cue light (CS(+)) or for water in the presence of anise odour (S(-)) and 1-s white noise (CS(-)), the effect of N/oFQ on cue-induced reinstatement of extinguished ethanol responding was investigated.


RESULTS
Sub-chronic (6 days) intracerebroventricular (i.c.v.) injection of 0.5 microg or 1.0 microg N/OFQ per rat significantly reduced alcohol self-administration under both the FR 1 and PR schedules of reinforcement. Conversely, i.c.v. administration of 0.5, 1.0 or 4.0 microg of the peptide per rat did not affect sucrose self-administration. In addition, i.c.v. N/OFQ (1.0-2.0 microg per rat) significantly inhibited the reinstatement of extinguished ethanol responding under an S(+)/CS(+) condition, whereas lever pressing under S(-)/CS(-) was not altered.


CONCLUSIONS
The present study demonstrates that the reinforcing effects of ethanol are markedly blunted by activation of the opioidergic N/OFQ receptor system. Moreover, the data provide evidence of the efficacy of N/OFQ to prevent reinstatement of ethanol-seeking behaviour elicited by environmental conditioned stimuli.
Ciccocioppo
Roberto
R
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Via Scalzino 3, 62032 Camerino, Italy. roberto.ciccocioppo@unicam.it
Economidou
Daina
D
Fedeli
Amalia
A
Angeletti
Stefania
S
Weiss
Friedbert
F
Heilig
Markus
M
Massi
Maurizio
M
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D008297:Male; D018847:Opioid Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology; D000097629:Nociceptin
D000431:Ethanol; D018847:Opioid Peptides; D000097629:Nociceptin