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Differential Role of D 1 and D 2 Receptors in the Perifornical Lateral Hypothalamus in Controlling Ethanol Drinking and Food Intake: Possible Interaction with Local Orexin Neurons
Author(s) -
Chen YuWei,
Morganstern Irene,
Barson Jessica R.,
Hoebel Bartley G.,
Leibowitz Sarah F.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12313
Subject(s) - agonist , chemistry , medicine , endocrinology , orexin , hypothalamus , dopaminergic , lateral hypothalamus , antagonist , sulpiride , nociceptin receptor , receptor , dopamine , neuropeptide , opioid , opioid peptide
Background The neurotransmitter dopamine ( DA ), acting in various mesolimbic brain regions, is well known for its role in promoting motivated behaviors, including ethanol (EtOH) drinking. Indirect evidence, however, suggests that DA in the perifornical lateral hypothalamus ( PF / LH ) has differential effects on EtOH consumption, depending on whether it acts on the DA 1 ( D 1) or DA 2 ( D 2) receptor subtype, and that these effects are mediated in part by local peptide systems, such as orexin/hypocretin ( OX ) and melanin‐concentrating hormone ( MCH ), known to stimulate the consumption of EtOH. Methods The present study in brain‐cannulated S prague‐ D awley rats measured the effects of dopaminergic compounds in the PF / LH on drinking behavior in animals trained to consume 7% EtOH and also on local peptide mRNA expression using digoxigenin‐labeled in situ hybridization in EtOH‐naïve animals. Results Experiments 1 and 2 showed that the D 1 agonist SK F81297 (10.8 nmol/side) in the PF / LH significantly increased food intake, while tending to increase EtOH intake, and the D 1 antagonist SCH 23390 significantly decreased EtOH intake without affecting food intake. In contrast, the D 2 agonist quinelorane (6.2 nmol/side) in the PF / LH significantly reduced EtOH consumption, while the D 2 antagonist sulpiride increased it. Experiments 3 and 4 revealed differential effects of PF / LH injection of the DA agonists on local OX mRNA , which was increased by the D 1 agonist and decreased by the D 2 agonist. These DA agonists had no impact on MCH expression. Conclusions These results support a stimulatory role of the PF / LH D 1 receptor in promoting the consumption of both EtOH and food, in contrast to a suppressive effect of the D 2 receptor on EtOH drinking. They further suggest that these receptors affect consumption, in part, through local OX ‐expressing neurons. These findings provide new evidence for the function of PF / LH DA receptor subtypes in controlling EtOH and food intake.