Cargando…
Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability
Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656565/ https://www.ncbi.nlm.nih.gov/pubmed/28439100 http://dx.doi.org/10.1038/mp.2017.80 |
_version_ | 1783273712623026176 |
---|---|
author | Miller, Michael L. Ren, Yanhua Szutorisz, Henrietta Warren, Noël A. Tessereau, Chloé Egervári, Gábor Mlodnicka, Agnieszka Kapoor, Manav Chaarani, Bader Morris, Claudia V. Schumann, Gunter Garavan, Hugh Goate, Alison M. Bannon, Michael J. Halperin, Jeffrey M. Hurd, Yasmin L. |
author_facet | Miller, Michael L. Ren, Yanhua Szutorisz, Henrietta Warren, Noël A. Tessereau, Chloé Egervári, Gábor Mlodnicka, Agnieszka Kapoor, Manav Chaarani, Bader Morris, Claudia V. Schumann, Gunter Garavan, Hugh Goate, Alison M. Bannon, Michael J. Halperin, Jeffrey M. Hurd, Yasmin L. |
author_sort | Miller, Michael L. |
collection | PubMed |
description | Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood. Here we report the critical role of ventral striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vulnerability. Using an ADHD rat model, we demonstrate that impulsive animals are neurochemically and behaviorally more sensitive to heroin and exhibit reduced Crem expression in the nucleus accumbens core. Virally increasing Crem levels decreased impulsive action, thus establishing a causal relationship. Genetic studies in seven independent human populations illustrate that a CREM promoter variant at rs12765063 is associated with impulsivity, hyperactivity and addiction-related phenotypes. We also reveal a role of Crem in regulating striatal structural plasticity. Together, these results highlight that ventral striatal CREM mediates impulsivity related to substance abuse and suggest that CREM and its regulated network may be promising therapeutic targets. |
format | Online Article Text |
id | pubmed-5656565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-56565652017-10-26 Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability Miller, Michael L. Ren, Yanhua Szutorisz, Henrietta Warren, Noël A. Tessereau, Chloé Egervári, Gábor Mlodnicka, Agnieszka Kapoor, Manav Chaarani, Bader Morris, Claudia V. Schumann, Gunter Garavan, Hugh Goate, Alison M. Bannon, Michael J. Halperin, Jeffrey M. Hurd, Yasmin L. Mol Psychiatry Article Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood. Here we report the critical role of ventral striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vulnerability. Using an ADHD rat model, we demonstrate that impulsive animals are neurochemically and behaviorally more sensitive to heroin and exhibit reduced Crem expression in the nucleus accumbens core. Virally increasing Crem levels decreased impulsive action, thus establishing a causal relationship. Genetic studies in seven independent human populations illustrate that a CREM promoter variant at rs12765063 is associated with impulsivity, hyperactivity and addiction-related phenotypes. We also reveal a role of Crem in regulating striatal structural plasticity. Together, these results highlight that ventral striatal CREM mediates impulsivity related to substance abuse and suggest that CREM and its regulated network may be promising therapeutic targets. 2017-04-25 2018-05 /pmc/articles/PMC5656565/ /pubmed/28439100 http://dx.doi.org/10.1038/mp.2017.80 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Miller, Michael L. Ren, Yanhua Szutorisz, Henrietta Warren, Noël A. Tessereau, Chloé Egervári, Gábor Mlodnicka, Agnieszka Kapoor, Manav Chaarani, Bader Morris, Claudia V. Schumann, Gunter Garavan, Hugh Goate, Alison M. Bannon, Michael J. Halperin, Jeffrey M. Hurd, Yasmin L. Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title | Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title_full | Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title_fullStr | Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title_full_unstemmed | Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title_short | Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability |
title_sort | ventral striatal regulation of crem mediates impulsive action and drug addiction vulnerability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656565/ https://www.ncbi.nlm.nih.gov/pubmed/28439100 http://dx.doi.org/10.1038/mp.2017.80 |
work_keys_str_mv | AT millermichaell ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT renyanhua ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT szutoriszhenrietta ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT warrennoela ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT tessereauchloe ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT egervarigabor ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT mlodnickaagnieszka ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT kapoormanav ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT chaaranibader ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT morrisclaudiav ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT schumanngunter ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT garavanhugh ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT goatealisonm ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT bannonmichaelj ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT halperinjeffreym ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability AT hurdyasminl ventralstriatalregulationofcremmediatesimpulsiveactionanddrugaddictionvulnerability |