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dc.contributor.author
Zhou, Yan
dc.contributor.author
Rubinstein, Marcelo
dc.contributor.author
Low, Malcolm J.
dc.contributor.author
Kreek, Mary Jeanne
dc.date.available
2018-03-12T20:58:32Z
dc.date.issued
2017-04
dc.identifier.citation
Zhou, Yan; Rubinstein, Marcelo; Low, Malcolm J.; Kreek, Mary Jeanne; Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice; Wiley Blackwell Publishing, Inc; Genes, Brain and Behavior; 16; 4; 4-2017; 449-461
dc.identifier.issn
1601-1848
dc.identifier.uri
http://hdl.handle.net/11336/38624
dc.description.abstract
Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in both humans and rodents. This study investigated whether hypothalamic proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE−/−), resulting in hypothalamic-specific POMC deficiency, were studied in short-access (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle, intermittent access (IA, 24-h cycles of alcohol access every other day, alcohol vs. water in a two-bottle choice) and alcohol deprivation effect (ADE) models. Wild-type nPE+/+ exposed to 1-week DID rapidly established stable alcohol drinking behavior with more intake in females, whereas nPE−/− mice of both sexes had less intake and less preference. Although nPE−/− showed less saccharin intake and preference than nPE+/+, there was no genotype difference in sucrose intake or preference in the DID paradigm. After 3-week IA, nPE+/+ gradually escalated to high alcohol intake and preference, with more intake in females, whereas nPE−/− showed less escalation. Pharmacological blockade of mu-opioid receptors with naltrexone reduced intake in nPE+/+ in a dose-dependent manner, but had blunted effects in nPE−/− of both sexes. When alcohol was presented again after 1-week abstinence from IA, nPE+/+ of both sexes displayed significant increases in alcohol intake (ADE or relapse-like drinking), with more pronounced ADE in females, whereas nPE−/− did not show ADE in either sex. Our results suggest that neuronal POMC is involved in modulation of alcohol ‘binge’ drinking, escalation and ‘relapse’, probably via hypothalamic-mediated mechanisms, with sex differences.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ALCOHOL DEPRIVATION EFFECT
dc.subject
DRINKING-IN-THE-DARK
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HYPOTHALAMIC-SPECIFIC POMC-DEFICIENT MICE
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INTERMITTENT ACCESS DRINKING
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NALTREXONE
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SEX DIFFERENCES
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-12T19:28:44Z
dc.journal.volume
16
dc.journal.number
4
dc.journal.pagination
449-461
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Zhou, Yan. The Rockefeller University; Estados Unidos
dc.description.fil
Fil: Rubinstein, Marcelo. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Low, Malcolm J.. University of Michigan; Estados Unidos
dc.description.fil
Fil: Kreek, Mary Jeanne. The Rockefeller University; Estados Unidos
dc.journal.title
Genes, Brain and Behavior
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/gbb.12362
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/gbb.12362/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/21649851/
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