title: Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.
abstract: BACKGROUND
  Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats.
  
  
  METHODS
  For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat).
  
  
  RESULTS
  Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals.
  
  
  CONCLUSIONS
  These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms.
authors.affiliation: Department of Experimental Medicine and Public Health, University of Camerino, Camerino, Italy.
authors.forename: Daina
authors.initials: D
authors.lastname: Economidou
authors.forename: Andrea
authors.initials: A
authors.lastname: Cippitelli
authors.forename: Serena
authors.initials: S
authors.lastname: Stopponi
authors.forename: Simone
authors.initials: S
authors.lastname: Braconi
authors.forename: Stefano
authors.initials: S
authors.lastname: Clementi
authors.forename: Massimo
authors.initials: M
authors.lastname: Ubaldi
authors.forename: Rèmi
authors.initials: R
authors.lastname: Martin-Fardon
authors.forename: Friedbert
authors.initials: F
authors.lastname: Weiss
authors.forename: Maurizio
authors.initials: M
authors.lastname: Massi
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
mesh_terms: D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001921:Brain; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D000094942:Nociceptin Receptor
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D018377:Neurotransmitter Agents; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; C466980:nociceptin orphanin FQ(1-17)OH; C000722285:Oprl1 protein, rat