The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure

Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associat...

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Main Authors:	Soares-Cunha, C, Coimbra, B, Borges, S, Carvalho, M M, Rodrigues, A J, Sousa, N
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080326/

id	pubmed-4080326
recordtype	oai_dc
spelling	pubmed-40803262014-07-09 The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure Soares-Cunha, C Coimbra, B Borges, S Carvalho, M M Rodrigues, A J Sousa, N Original Article Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical. Nature Publishing Group 2014-06 2014-06-10 /pmc/articles/PMC4080326/ /pubmed/25928947 http://dx.doi.org/10.1038/tp.2014.45 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Soares-Cunha, C Coimbra, B Borges, S Carvalho, M M Rodrigues, A J Sousa, N
spellingShingle	Soares-Cunha, C Coimbra, B Borges, S Carvalho, M M Rodrigues, A J Sousa, N The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
author_facet	Soares-Cunha, C Coimbra, B Borges, S Carvalho, M M Rodrigues, A J Sousa, N
author_sort	Soares-Cunha, C
title	The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
title_short	The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
title_full	The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
title_fullStr	The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
title_full_unstemmed	The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
title_sort	motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure
description	Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080326/
_version_	1612109378642509824

The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure

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