Cargando…

Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry

Early adverse experience is a well-known risk factor for addictive behaviors later in life. Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC). While it has been shown that dopaminergic modulation within the PFC is involved in addictio...

Descripción completa

Detalles Bibliográficos
Autores principales: Brenhouse, Heather C., Lukkes, Jodi L., Andersen, Susan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061828/
https://www.ncbi.nlm.nih.gov/pubmed/24961311
http://dx.doi.org/10.3390/brainsci3010143
_version_ 1782321556412694528
author Brenhouse, Heather C.
Lukkes, Jodi L.
Andersen, Susan L.
author_facet Brenhouse, Heather C.
Lukkes, Jodi L.
Andersen, Susan L.
author_sort Brenhouse, Heather C.
collection PubMed
description Early adverse experience is a well-known risk factor for addictive behaviors later in life. Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC). While it has been shown that dopaminergic modulation within the PFC is involved in addiction-like behaviors, little is known about how early adversity modulates its development. Here, we report that maternal separation stress (4 h per day between postnatal days 2–20) alters the development of the prelimbic PFC. Immunofluorescence and confocal microscopy revealed differences between maternally-separated and control rats in dopamine D1 and D2 receptor expression during adolescence, and specifically the expression of these receptors on projection neurons. In control animals, D1 and D2 receptors were transiently increased on all glutamatergic projection neurons, as well as specifically on PFC→nucleus accumbens projection neurons (identified with retrograde tracer). Maternal separation exacerbated the adolescent peak in D1 expression and blunted the adolescent peak in D2 expression on projection neurons overall. However, neurons retrogradely traced from the accumbens expressed lower levels of D1 during adolescence after maternal separation, compared to controls. Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence.
format Online
Article
Text
id pubmed-4061828
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-40618282014-06-19 Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry Brenhouse, Heather C. Lukkes, Jodi L. Andersen, Susan L. Brain Sci Article Early adverse experience is a well-known risk factor for addictive behaviors later in life. Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC). While it has been shown that dopaminergic modulation within the PFC is involved in addiction-like behaviors, little is known about how early adversity modulates its development. Here, we report that maternal separation stress (4 h per day between postnatal days 2–20) alters the development of the prelimbic PFC. Immunofluorescence and confocal microscopy revealed differences between maternally-separated and control rats in dopamine D1 and D2 receptor expression during adolescence, and specifically the expression of these receptors on projection neurons. In control animals, D1 and D2 receptors were transiently increased on all glutamatergic projection neurons, as well as specifically on PFC→nucleus accumbens projection neurons (identified with retrograde tracer). Maternal separation exacerbated the adolescent peak in D1 expression and blunted the adolescent peak in D2 expression on projection neurons overall. However, neurons retrogradely traced from the accumbens expressed lower levels of D1 during adolescence after maternal separation, compared to controls. Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence. MDPI 2013-02-04 /pmc/articles/PMC4061828/ /pubmed/24961311 http://dx.doi.org/10.3390/brainsci3010143 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Brenhouse, Heather C.
Lukkes, Jodi L.
Andersen, Susan L.
Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title_full Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title_fullStr Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title_full_unstemmed Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title_short Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
title_sort early life adversity alters the developmental profiles of addiction-related prefrontal cortex circuitry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4061828/
https://www.ncbi.nlm.nih.gov/pubmed/24961311
http://dx.doi.org/10.3390/brainsci3010143
work_keys_str_mv AT brenhouseheatherc earlylifeadversityaltersthedevelopmentalprofilesofaddictionrelatedprefrontalcortexcircuitry
AT lukkesjodil earlylifeadversityaltersthedevelopmentalprofilesofaddictionrelatedprefrontalcortexcircuitry
AT andersensusanl earlylifeadversityaltersthedevelopmentalprofilesofaddictionrelatedprefrontalcortexcircuitry