Perinatal interference with the serotonergic system affects VTA function in the adult via glutamate co-transmission.
Mol Psychiatry
; 26(9): 4795-4812, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-32398719
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Área Tegmentar Ventral
/
Ácido Glutâmico
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Mol Psychiatry
Ano de publicação:
2021
Tipo de documento:
Article