The metabotropic glutamate receptor 2/3 antagonist LY341495 improves working memory in adult mice following juvenile social isolation.
Age Factors
Amino Acids
/ pharmacology
Animals
Excitatory Amino Acid Antagonists
/ pharmacology
Excitatory Postsynaptic Potentials
/ drug effects
Male
Maze Learning
/ drug effects
Memory, Short-Term
/ drug effects
Mice
Mice, Inbred C57BL
Receptors, Metabotropic Glutamate
/ antagonists & inhibitors
Social Isolation
/ psychology
Xanthenes
/ pharmacology
Cognitive deficits
Excitatory synaptic transmission
Metabotropic glutamate receptors
Social isolation
Journal
Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
13
02
2020
revised:
26
05
2020
accepted:
04
07
2020
pubmed:
22
7
2020
medline:
13
8
2021
entrez:
22
7
2020
Statut:
ppublish
Résumé
Juvenile social isolation (SI) and neglect have a negative impact on neurodevelopment persistently, which is associated with cognitive dysfunction in neurodevelopmental disorders. Given the critical role of metabotropic glutamate receptors (mGluRs) in synaptic homeostasis of the prefrontal cortex (PFC), pharmacological intervention on mGluRs has been attempted in order to improve cognitive dysfunction in animal models of neurodevelopmental disorder, as well as in clinical trials. Here we examined the effects of the mGluR2/3 antagonist LY341495 on prefrontal synaptic transmission, spatial working memory, and recognition memory in adult C57BL/6J mice that experienced juvenile SI. We found that SI-reared mice exhibited working memory impairment and decreased excitatory presynaptic release probability of pyramidal neurons in the medial PFC compared with group-reared mice. The positive effect of LY341495 on excitatory synaptic transmission in SI-reared mice was more prominent than the effect in group-reared mice. A single treatment with mGluR2/3 antagonist LY341495 significantly improved the performance of SI-reared mice in the Y-maze test but not in the novel object recognition (NOR) test, while repeated treatments were effective in both tasks. These findings suggest that enhancing glutamatergic transmission via inhibition of mGluR2/3 signaling might represent a promising strategy for improving cognitive function in neurodevelopmental disorders.
Identifiants
pubmed: 32693006
pii: S0028-3908(20)30299-9
doi: 10.1016/j.neuropharm.2020.108231
pii:
doi:
Substances chimiques
Amino Acids
0
Excitatory Amino Acid Antagonists
0
LY 341495
0
Receptors, Metabotropic Glutamate
0
Xanthenes
0
metabotropic glutamate receptor 2
0
metabotropic glutamate receptor 3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108231Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.