Producción CyT

Severe serotonin depletion after conditional deletion of the vesicular monoamine transporter 2 gene in serotonin neurons: neural and behavioral consequences

Articulo

Autoría:

Narboux-Nême N ; Sagné C ; Doly S ; DIAZ, SILVINA LAURA ; Martin CBP ; Angenard G ; Martres MP ; Giros B ; Hamon M ; Lanfumey L ; Gaspar P ; Mongeau R

Fecha:

2011

Editorial y Lugar de Edición:

NATURE PUBLISHING GROUP

Revista:

NEUROPSYCHOPHARMACOLOGY, vol. 36 (pp. 2538-2550) NATURE PUBLISHING GROUP

Resumen *

The vesicular monoamine transporter type 2 gene (VMAT2) has a crucial role in the storage and synaptic release of all monoamines, including serotonin (5-HT). To evaluate the specific role of VMAT2 in 5-HT neurons, we produced a conditional ablation of VMAT2 under control of the serotonin transporter (slc6a4) promoter. vMAT2sert_cre mice showed a major (_95%) depletion of 5-HT levels in the brain with no major alterations in other monoamines. Raphe neurons contained no 5-HT immunoreactivity in VMAT2sert_cre mice but developed normal innervations, as assessed by both tryptophan hydroxylase 2 and 5-HT transporter labeling. Increased 5-HT1A autoreceptor coupling to G protein, as assessed with agonist-stimulated [35S]GTP-g-S binding, was observed in the raphe area, indicating an adaptive change to reduced 5-HT transmission. Behavioral evaluation in adult VMAT2sert_cre mice showed an increase in escape-like reactions in response to tail suspension and anxiolytic-like response in the novelty-suppressed feeding test. In an aversive ultrasoundinduced defense paradigm, vMAT2sert_cre mice displayed a major increase in escape-like behaviors. Wild-type-like defense phenotype could be rescued by replenishing intracellular 5-HT stores with chronic pargyline (a monoamine oxidase inhibitor) treatment. Pargyline also allowed some form of 5-HT release, although in reduced amounts, in synaptosomes from VMAT2sert_cre mouse brain. These findings are coherent with the notion that 5-HT has an important role in anxiety, and provide new insights into the role of endogenous 5-HT in defense behaviors. Información suministrada por el agente en SIGEVA

Palabras Clave

DEPRESSIONSEROTONIN TRANSPORTERDEFENSE BEHAVIORSCONDITIONAL KNOCKOUT MICERAPHEANXIETY