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Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience

We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16–19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA funct...

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Autores principales: Virdee, Kanwar, McArthur, Simon, Brischoux, Frédéric, Caprioli, Daniele, Ungless, Mark A, Robbins, Trevor W, Dalley, Jeffrey W, Gillies, Glenda E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870772/
https://www.ncbi.nlm.nih.gov/pubmed/23929547
http://dx.doi.org/10.1038/npp.2013.196
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author Virdee, Kanwar
McArthur, Simon
Brischoux, Frédéric
Caprioli, Daniele
Ungless, Mark A
Robbins, Trevor W
Dalley, Jeffrey W
Gillies, Glenda E
author_facet Virdee, Kanwar
McArthur, Simon
Brischoux, Frédéric
Caprioli, Daniele
Ungless, Mark A
Robbins, Trevor W
Dalley, Jeffrey W
Gillies, Glenda E
author_sort Virdee, Kanwar
collection PubMed
description We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16–19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA function in adult rats. We show that in adulthood, enrichment of striatal DA fiber density paralleled AGT-induced increases in the numbers of midbrain DA neurons, which retained normal basal electrophysiological properties. This was co-incident with changes in (i) striatal D(2)-type receptor levels (increased, both sexes); (ii) D(1)-type receptor levels (males decreased; females increased); (iii) DA transporter levels (males increased; females decreased) in striatal regions; and (iv) amphetamine-induced mesolimbic DA release (males increased; females decreased). However, despite these profound, sexually dimorphic changes in markers of DA neurotransmission, in-utero glucocorticoid overexposure had a modest or no effect on a range of conditioned and unconditioned appetitive behaviors known to depend on mesolimbic DA activity. These findings provide empirical evidence for enduring AGT-induced adaptive mechanisms within the midbrain DA circuitry, which preserve some, but not all, functions, thereby casting further light on the vulnerability of these systems to environmental perturbations. Furthermore, they demonstrate these effects are achieved by different, often opponent, adaptive mechanisms in males and females, with translational implications for sex biases commonly found in midbrain DA-associated disorders.
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spelling pubmed-38707722014-01-01 Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience Virdee, Kanwar McArthur, Simon Brischoux, Frédéric Caprioli, Daniele Ungless, Mark A Robbins, Trevor W Dalley, Jeffrey W Gillies, Glenda E Neuropsychopharmacology Original Article We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16–19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA function in adult rats. We show that in adulthood, enrichment of striatal DA fiber density paralleled AGT-induced increases in the numbers of midbrain DA neurons, which retained normal basal electrophysiological properties. This was co-incident with changes in (i) striatal D(2)-type receptor levels (increased, both sexes); (ii) D(1)-type receptor levels (males decreased; females increased); (iii) DA transporter levels (males increased; females decreased) in striatal regions; and (iv) amphetamine-induced mesolimbic DA release (males increased; females decreased). However, despite these profound, sexually dimorphic changes in markers of DA neurotransmission, in-utero glucocorticoid overexposure had a modest or no effect on a range of conditioned and unconditioned appetitive behaviors known to depend on mesolimbic DA activity. These findings provide empirical evidence for enduring AGT-induced adaptive mechanisms within the midbrain DA circuitry, which preserve some, but not all, functions, thereby casting further light on the vulnerability of these systems to environmental perturbations. Furthermore, they demonstrate these effects are achieved by different, often opponent, adaptive mechanisms in males and females, with translational implications for sex biases commonly found in midbrain DA-associated disorders. Nature Publishing Group 2014-01 2013-09-11 /pmc/articles/PMC3870772/ /pubmed/23929547 http://dx.doi.org/10.1038/npp.2013.196 Text en Copyright © 2014 American College of Neuropsychopharmacology http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
Virdee, Kanwar
McArthur, Simon
Brischoux, Frédéric
Caprioli, Daniele
Ungless, Mark A
Robbins, Trevor W
Dalley, Jeffrey W
Gillies, Glenda E
Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title_full Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title_fullStr Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title_full_unstemmed Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title_short Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience
title_sort antenatal glucocorticoid treatment induces adaptations in adult midbrain dopamine neurons, which underpin sexually dimorphic behavioral resilience
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870772/
https://www.ncbi.nlm.nih.gov/pubmed/23929547
http://dx.doi.org/10.1038/npp.2013.196
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