Document Detail

Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat.
MedLine Citation:
PMID:  18367152     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Alcoholism is a complex behavioral disorder in which interactions between stressful life events and heritable susceptibility factors contribute to the initiation and progression of disease. Neural substrates of these interactions remain largely unknown. Here, we examined the role of the nociceptin/orphanin FQ (N/OFQ) system, with an animal model in which genetic selection for high alcohol preference has led to co-segregation of elevated behavioral sensitivity to stress (Marchigian Sardinian alcohol-preferring [msP]).
METHODS: The msP and Wistar rats trained to self-administer alcohol received central injections of N/OFQ. In situ hybridization and receptor binding assays were also performed to evaluate N/OFQ receptor (NOP) function in naïve msP and Wistar rats.
RESULTS: Intracerebroventricular (ICV) injection of N/OFQ significantly inhibited alcohol self-administration in msP but not in nonselected Wistar rats. The NOP receptor messenger RNA expression and binding was upregulated across most brain regions in msP compared with Wistar rats. However, in msP rats [(35)S]GTPgammaS binding revealed a selective impairment of NOP receptor signaling in the central amygdala (CeA). Ethanol self-administration in msP rats was suppressed after N/OFQ microinjection into the CeA but not into the bed nucleus of the stria terminalis or the basolateral amygdala.
CONCLUSIONS: These findings indicate that dysregulation of N/OFQ-NOP receptor signaling in the CeA contributes to excessive alcohol intake in msP rats and that this phenotype can be rescued by local administration of pharmacological doses of exogenous N/OFQ. Data are interpreted on the basis of the anti-corticotropin releasing factor (CRF) actions of N/OFQ and the significance of the CRF system in promoting excessive alcohol drinking in msP rats.
Daina Economidou; Anita C Hansson; Friedbert Weiss; Anton Terasmaa; Wolfgang H Sommer; Andrea Cippitelli; Amalia Fedeli; Rèmi Martin-Fardon; Maurizio Massi; Roberto Ciccocioppo; Markus Heilig
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-03-25
Journal Detail:
Title:  Biological psychiatry     Volume:  64     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-11     Completed Date:  2008-10-07     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  211-8     Citation Subset:  IM    
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MeSH Terms
Alcohol Drinking / genetics,  pathology*,  psychology
Amygdala / drug effects,  metabolism*
Analysis of Variance
Autoradiography / methods
Behavior, Animal
Central Nervous System Depressants / administration & dosage*
Ethanol / administration & dosage*
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Injections, Intraventricular
Motor Activity / drug effects
Opioid Peptides / metabolism*,  pharmacology
Rats, Wistar
Receptors, Opioid / genetics,  metabolism
Reinforcement Schedule
Self Administration / psychology
Vasodilator Agents / metabolism*,  pharmacology
Grant Support
Reg. No./Substance:
0/Central Nervous System Depressants; 0/Opioid Peptides; 0/Receptors, Opioid; 0/Vasodilator Agents; 0/nociceptin; 0/nociceptin receptor; 37589-80-3/Guanosine 5'-O-(3-Thiotriphosphate); 3K9958V90M/Ethanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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