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Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission
Serotonin and dopamine are associated with multiple psychiatric disorders. How they interact during development to affect subsequent behavior remains unknown. Knockout of the serotonin transporter or postnatal blockade with selective-serotonin-reuptake inhibitors (SSRIs) leads to novelty-induced exp...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657958/ https://www.ncbi.nlm.nih.gov/pubmed/32398719 http://dx.doi.org/10.1038/s41380-020-0763-z |
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author | Cunha, Catarina Smiley, John F. Chuhma, Nao Shah, Relish Bleiwas, Cynthia Menezes, Edenia C. Seal, Rebecca P. Edwards, Robert H. Rayport, Stephen Ansorge, Mark S. Castellanos, Francisco X. Teixeira, Catia M. |
author_facet | Cunha, Catarina Smiley, John F. Chuhma, Nao Shah, Relish Bleiwas, Cynthia Menezes, Edenia C. Seal, Rebecca P. Edwards, Robert H. Rayport, Stephen Ansorge, Mark S. Castellanos, Francisco X. Teixeira, Catia M. |
author_sort | Cunha, Catarina |
collection | PubMed |
description | Serotonin and dopamine are associated with multiple psychiatric disorders. How they interact during development to affect subsequent behavior remains unknown. Knockout of the serotonin transporter or postnatal blockade with selective-serotonin-reuptake inhibitors (SSRIs) leads to novelty-induced exploration deficits in adulthood, potentially involving the dopamine system. Here we show in the mouse that raphe nucleus serotonin neurons activate ventral tegmental area dopamine neurons via glutamate co-transmission and that this co-transmission is reduced in animals exposed postnatally to SSRIs. Blocking serotonin neuron glutamate co-transmission mimics this SSRI-induced hypolocomotion, while optogenetic activation of dopamine neurons reverses this hypolocomotor phenotype. Our data demonstrate that serotonin neurons modulate dopamine neuron activity via glutamate co-transmission and that this pathway is developmentally malleable, with high serotonin levels during early life reducing co-transmission, revealing the basis for the reduced novelty-induced exploration in adulthood due to postnatal SSRI exposure. |
format | Online Article Text |
id | pubmed-7657958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76579582021-11-12 Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission Cunha, Catarina Smiley, John F. Chuhma, Nao Shah, Relish Bleiwas, Cynthia Menezes, Edenia C. Seal, Rebecca P. Edwards, Robert H. Rayport, Stephen Ansorge, Mark S. Castellanos, Francisco X. Teixeira, Catia M. Mol Psychiatry Article Serotonin and dopamine are associated with multiple psychiatric disorders. How they interact during development to affect subsequent behavior remains unknown. Knockout of the serotonin transporter or postnatal blockade with selective-serotonin-reuptake inhibitors (SSRIs) leads to novelty-induced exploration deficits in adulthood, potentially involving the dopamine system. Here we show in the mouse that raphe nucleus serotonin neurons activate ventral tegmental area dopamine neurons via glutamate co-transmission and that this co-transmission is reduced in animals exposed postnatally to SSRIs. Blocking serotonin neuron glutamate co-transmission mimics this SSRI-induced hypolocomotion, while optogenetic activation of dopamine neurons reverses this hypolocomotor phenotype. Our data demonstrate that serotonin neurons modulate dopamine neuron activity via glutamate co-transmission and that this pathway is developmentally malleable, with high serotonin levels during early life reducing co-transmission, revealing the basis for the reduced novelty-induced exploration in adulthood due to postnatal SSRI exposure. 2020-05-12 2021-09 /pmc/articles/PMC7657958/ /pubmed/32398719 http://dx.doi.org/10.1038/s41380-020-0763-z 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 Cunha, Catarina Smiley, John F. Chuhma, Nao Shah, Relish Bleiwas, Cynthia Menezes, Edenia C. Seal, Rebecca P. Edwards, Robert H. Rayport, Stephen Ansorge, Mark S. Castellanos, Francisco X. Teixeira, Catia M. Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title | Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title_full | Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title_fullStr | Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title_full_unstemmed | Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title_short | Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission |
title_sort | perinatal interference with the serotonergic system affects vta function in the adult via glutamate co-transmission |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657958/ https://www.ncbi.nlm.nih.gov/pubmed/32398719 http://dx.doi.org/10.1038/s41380-020-0763-z |
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