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Glutamatergic input to the lateral hypothalamus stimulates ethanol intake: role of orexin and melanin-concentrating hormone
Journal article   Open access   Peer reviewed

Glutamatergic input to the lateral hypothalamus stimulates ethanol intake: role of orexin and melanin-concentrating hormone

Yu-Wei Chen, Jessica R Barson, Aimee Chen, Bartley G Hoebel and Sarah F Leibowitz
Alcoholism, clinical and experimental research, v 37(1)
Jan 2013
DOI: https://doi.org/10.1111/j.1530-0277.2012.01854.x
PMID: 22823322
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4007270View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Alcohol Drinking - metabolism alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - agonists alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - antagonists & inhibitors alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism Animals Glutamic Acid - metabolism Hypothalamic Area, Lateral - metabolism Hypothalamic Hormones - metabolism Intracellular Signaling Peptides and Proteins - metabolism Male Melanins - metabolism N-Methylaspartate - agonists N-Methylaspartate - antagonists & inhibitors N-Methylaspartate - metabolism Neuropeptides - metabolism Orexins Pituitary Hormones - metabolism Rats Rats, Sprague-Dawley
Glutamate (GLUT) in the lateral hypothalamus (LH) has been suggested to mediate reward behaviors and may promote the ingestion of drugs of abuse. This study tested the hypothesis that GLUT in the LH stimulates consumption of ethanol ( EtOH ) and that this effect occurs, in part, via its interaction with local peptides, hypocretin/orexin (OX), and melanin-concentrating hormone (MCH). In Experiments 1 and 2, male Sprague-Dawley rats, after being trained to drink 9% EtOH , were microinjected in the LH with N-methyl-d-aspartate (NMDA) or its antagonist, D-AP5, or with alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid (AMPA) or its antagonist, CNQX-ds. Consumption of EtOH , chow, and water was then measured. To provide an anatomical control, a separate set of rats was injected 2 mm dorsal to the LH. In Experiment 3, the effect of LH injection of NMDA and AMPA on the expression of OX and MCH was measured using radiolabeled in situ hybridization (ISH) and also using digoxigenin-labeled ISH, to distinguish effects on OX and MCH cells in the LH and the nearby perifornical area (PF) and zona incerta (ZI). When injected into the LH, NMDA and AMPA both significantly increased EtOH intake while having no effect on chow or water intake. The GLUT receptor antagonists had the opposite effect, significantly reducing EtOH consumption. No effects were observed with injections 2 mm dorsal to the LH. In addition to these behavioral effects, LH injection of NMDA significantly stimulated expression of OX in both the LH and PF while reducing MCH in the ZI, whereas AMPA increased OX only in the LH and had no effect on MCH. Glutamatergic inputs to the LH, acting through NMDA and AMPA receptors, appear to have a stimulatory effect on EtOH consumption, mediated in part by increased OX in LH and PF and reduced MCH in ZI.

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14 citations in Web of Science
17 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Substance Abuse
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