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Context and topography determine the role of basolateral amygdala metabotropic glutamate receptor 5 in appetitive Pavlovian responding

Title:

Context and topography determine the role of basolateral amygdala metabotropic glutamate receptor 5 in appetitive Pavlovian responding

Khoo, Shaun Yon-Seng ORCID: https://orcid.org/0000-0002-0972-3788, LeCocq, Mandy Rita, Deyab, Ghislaine E. and Chaudhri, Nadia ORCID: https://orcid.org/0000-0003-4217-4044 (2019) Context and topography determine the role of basolateral amygdala metabotropic glutamate receptor 5 in appetitive Pavlovian responding. Neuropsychopharmacology . ISSN 1740-634X

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Abstract

Preclinical data have shown that the excitatory metabotropic Gαq-coupled glutamate receptor, mGluR5, has a role in substance abuse and relapse. However, little is known about the contribution of mGluR5 to the expression of conditioned responding elicited by appetitive Pavlovian cues. We investigated this question in rats that were trained to associate a discrete, auditory conditioned stimulus (CS) with a fructose-glucose solution (5.5% fructose/4.5% glucose; ‘sugar’). In subsequent tests for the expression of conditioned responding without sugar delivery, CS-elicited fluid port entries were elevated in a context associated with sugar, relative to an equally familiar, neutral context. Inhibiting mGluR5 via systemic injections of a negative allosteric modulator (MTEP; 5 mg/kg) reduced CS port entries in both the sugar context and neutral context. Targeting MTEP microinjections (3 µg/side; 0.3 µl/min) to the nucleus accumbens (Acb) core had no effect on CS port entries at test, whereas the same manipulation in the basolateral amygdala (BLA) produced effects that were topographically dependent. Specifically, microinjecting MTEP in the posterior BLA had no effect on behavior, whereas inhibiting mGluR5 in the anterior BLA enhanced the contextual discrimination of CS port entries. These data are the first to show a role of mGluR5 in the context-dependent expression of appetitive Pavlovian conditioned responding, with a topographically defined arrangement of mGluR5 in the BLA being particularly important for context-based responding to a discrete, appetitive cue.

Divisions:Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology
Item Type:Article
Refereed:Yes
Authors:Khoo, Shaun Yon-Seng and LeCocq, Mandy Rita and Deyab, Ghislaine E. and Chaudhri, Nadia
Journal or Publication:Neuropsychopharmacology
Date:February 2019
Funders:
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council
  • Fonds de la recherche du Québec
  • Concordia Horizon Postodoctoral Fellowship
  • Graduate Fellowship, Faculty of Arts and Science, Concordia University
Digital Object Identifier (DOI):10.1038/s41386-019-0335-6
Keywords:glutamate, mGlu5, GRM5, Pavlovian conditioning, sugar, addiction, context, cue, MK-801, NMDA, reinstatement, goal-tracking
ID Code:984953
Deposited By: SHAUN YON-SENG KHOO
Deposited On:12 Feb 2019 22:05
Last Modified:08 Aug 2019 00:00
Related URLs:
Additional Information:This is a post-peer-review, pre-copyedit version of an article published in Neuropsychopharmacology. The final authenticated version is available at: https://doi.org/10.1038/s41386-019-0335-6 Readers may also access the final version using the author's share link: https://rdcu.be/blQSk

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