In utero exposure to cocaine delays postnatal synaptic maturation of glutamatergic transmission in the VTA.

Détails

ID Serval
serval:BIB_50F14DB5C777
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In utero exposure to cocaine delays postnatal synaptic maturation of glutamatergic transmission in the VTA.
Périodique
Nature neuroscience
Auteur(s)
Bellone C., Mameli M., Lüscher C.
ISSN
1546-1726 (Electronic)
ISSN-L
1097-6256
Statut éditorial
Publié
Date de publication
02/10/2011
Peer-reviewed
Oui
Volume
14
Numéro
11
Pages
1439-1446
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Maternal exposure to cocaine may perturb fetal development and affect synaptic maturation in the offspring. However, the molecular mechanism underlying such changes remains elusive. We focused on the postnatal maturation of glutamatergic transmission onto ventral tegmental area dopamine neurons in the mouse. We found that, during the first postnatal week, transmission was dominated by calcium-permeable AMPA receptors and GluN2B-containing NMDA receptors. Subsequently, mGluR1 receptors drove synaptic insertion of calcium-impermeable AMPA receptors and GluN2A-containing NMDAR. When pregnant mice were exposed to cocaine, this glutamate receptor switch was delayed in offspring as a result of a direct effect of cocaine on the fetal dopamine transporter and impaired mGluR1 function. Finally, positive modulation of mGluR1 in vivo was sufficient to rescue maturation. These data identify the molecular target through which in utero cocaine delays postnatal synaptic maturation, reveal the underlying expression mechanism of this impairment and propose a potential rescue strategy.

Mots-clé
Age Factors, Anesthetics, Local/pharmacology, Animals, Animals, Newborn, Biophysics, Calcium/metabolism, Calcium Channel Blockers/pharmacology, Chelating Agents/pharmacology, Cocaine/pharmacology, Dopamine/metabolism, Dopamine/pharmacology, Dopamine Agents/pharmacology, Dopamine Plasma Membrane Transport Proteins/genetics, Dose-Response Relationship, Drug, Egtazic Acid/analogs & derivatives, Egtazic Acid/pharmacology, Electric Stimulation, Estrenes/pharmacology, Excitatory Amino Acid Agents/pharmacology, Excitatory Postsynaptic Potentials/drug effects, Excitatory Postsynaptic Potentials/physiology, Female, Gene Expression Regulation, Developmental/drug effects, Glutamic Acid/metabolism, In Vitro Techniques, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons/drug effects, Neurons/physiology, Nicotinic Antagonists/pharmacology, Patch-Clamp Techniques/methods, Phosphodiesterase Inhibitors/pharmacology, Polyamines/pharmacology, Pregnancy, Prenatal Exposure Delayed Effects/physiopathology, Pyrrolidinones/pharmacology, Receptors, Glutamate/metabolism, Receptors, Metabotropic Glutamate/genetics, Receptors, Metabotropic Glutamate/physiology, Synapses/drug effects, Synapses/physiology, Synaptic Transmission/drug effects, Synaptic Transmission/physiology, Time Factors, Ventral Tegmental Area/cytology, Ventral Tegmental Area/drug effects, Ventral Tegmental Area/growth & development
Pubmed
Web of science
Création de la notice
31/01/2017 16:19
Dernière modification de la notice
03/03/2018 17:10
Données d'usage