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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Opioids in the perifornical lateral hypothalamus suppress ethanol drinking
Alcohol (Fayetteville, N.Y.), v 47(1), pp 31-38
28 Nov 2012
PMID: 23199698
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The opioid system is known to enhance motivated behaviors, including ethanol drinking and food ingestion, by acting in various reward-related brain regions, such as the nucleus accumbens, ventral tegmental area and medial hypothalamus. There is indirect evidence, however, suggesting that opioid peptides may act differently in the perifornical lateral hypothalamus (PF/LH), causing a suppression of consummatory behavior. Using brain-cannulated Sprague-Dawley rats trained to voluntarily drink 7% ethanol, the present study tested the hypothesis that opioids in the PF/LH can reduce the consumption of ethanol, with animals receiving PF/LH injections of the δ-opioid receptor agonist D-Ala2-met-enkephalinamide (DALA), the µ-receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), the κ-receptor agonist (±)-trans-U-50,488 methanesulfonate (U-50,488H), or the general opioid antagonist methylated naloxone (m-naloxone). The consumption of ethanol, lab chow, and water was monitored for 4 hours after injection. The results showed that the three opioid receptor agonists injected into the PF/LH specifically and significantly reduced ethanol intake, while causing little change in chow or water intake, and the opposite effect, enhanced ethanol intake, was observed with the opioid antagonist. Of the three opioid agonists, the δ-agonist appears to produce the most consistent and long-lasting suppression of consumption. This effect was not observed with injections 2 mm dorsal to this area, focusing attention on the PF/LH as the main site of action. These results suggest that the opioid peptides have a specific role in the PF/LH of reducing ethanol drinking, which is distinct from their more commonly observed appetitive actions in other brain areas. The additional finding, that m-naloxone in the PF/LH stimulates ethanol intake in contrast to its generally suppressive effect in other regions, focuses attention on this hypothalamic area and its distinctive role in contributing to the variable effects sometimes observed with opioid antagonist therapy for alcoholism.
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Details
- Title
- Opioids in the perifornical lateral hypothalamus suppress ethanol drinking
- Creators
- Yu-Wei Chen - Rockefeller UniversityJessica R. Barson - Rockefeller UniversityAimee Chen - Princeton UniversityBartley G. Hoebel - Princeton UniversitySarah F. Leibowitz - Rockefeller University
- Publication Details
- Alcohol (Fayetteville, N.Y.), v 47(1), pp 31-38
- Publisher
- Elsevier
- Grant note
- R01 AA012882 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Web of Science ID
- WOS:000314489700008
- Scopus ID
- 2-s2.0-84872413644
- Other Identifier
- 991020100080604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy
- Substance Abuse
- Toxicology