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A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons.

Chu Sin Chung, P; Keyworth, HL; Martin-Garcia, E; Charbogne, P; Darcq, E; Bailey, A; Filliol, D; Matifas, A; Scherrer, G; Ouagazzal, AM; et al. Chu Sin Chung, P; Keyworth, HL; Martin-Garcia, E; Charbogne, P; Darcq, E; Bailey, A; Filliol, D; Matifas, A; Scherrer, G; Ouagazzal, AM; Gaveriaux-Ruff, C; Befort, K; Maldonado, R; Kitchen, I; Kieffer, BL (2015) A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons. Biological Psychiatry, 77 (4). pp. 404-415. ISSN 1873-2402 https://doi.org/10.1016/j.biopsych.2014.07.033
SGUL Authors: Bailey, Alexis

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Abstract

BACKGROUND: The delta opioid receptor (DOR) is broadly expressed throughout the nervous system; it regulates chronic pain, emotional responses, motivation, and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. We used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain. METHODS: We characterized DOR distribution in the brain of Dlx5/6-CreXOprd1(fl/fl) (Dlx-DOR) mice and tested main central DOR functions through behavioral testing. RESULTS: The DOR proteins were strongly deleted in olfactory bulb and striatum and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity, and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. The Dlx-DOR mice showed lower levels of anxiety in the elevated plus maze, opposing the known high anxiety in constitutive DOR knockout animals. Also, Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos protein staining after novelty suppressed feeding was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice. CONCLUSIONS: We demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. In emotional responses, DORs exert dual anxiolytic and anxiogenic roles, both of which may have implications in the area of anxiety disorders.

Item Type: Article
Additional Information: © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Conditional gene knockout, Delta opioid receptor, Emotion, GABAergic forebrain neurons, Locomotion, Motivation, Animals, Anxiety, Behavior, Animal, Benzamides, Benzazepines, Brain, Corpus Striatum, Dopamine Agonists, Female, GABAergic Neurons, Male, Mice, Mice, Knockout, Motivation, Motor Activity, Olfactory Bulb, Piperazines, Prosencephalon, Proto-Oncogene Proteins c-fos, RNA, Messenger, Receptors, Dopamine D1, Receptors, Opioid, delta, Brain, Olfactory Bulb, Prosencephalon, Corpus Striatum, Animals, Mice, Knockout, Mice, Benzamides, Piperazines, Benzazepines, Proto-Oncogene Proteins c-fos, Receptors, Dopamine D1, Receptors, Opioid, delta, RNA, Messenger, Dopamine Agonists, Behavior, Animal, Motor Activity, Anxiety, Motivation, Female, Male, GABAergic Neurons, Psychiatry, 06 Biological Sciences, 17 Psychology And Cognitive Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Biological Psychiatry
ISSN: 1873-2402
Language: eng
Dates:
DateEvent
15 February 2015Published
27 August 2014Published Online
24 July 2014Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
P50 DA005010National Institute on Drug Abusehttp://dx.doi.org/10.13039/100000026
U01 AA016658National Institute on Alcohol Abuse and Alcoholismhttp://dx.doi.org/10.13039/100000027
PubMed ID: 25444168
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108006
Publisher's version: https://doi.org/10.1016/j.biopsych.2014.07.033

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