Cargando…

The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice

Group II metabotropic glutamate receptor agonists have been suggested as potential anti‐psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non‐competitive N‐methyl‐d‐aspartate receptor (NMDAR) antagonists, including sp...

Descripción completa

Detalles Bibliográficos
Autores principales: Boerner, Thomas, Bygrave, Alexei M., Chen, Jingkai, Fernando, Anushka, Jackson, Stephanie, Barkus, Chris, Sprengel, Rolf, Seeburg, Peter H., Harrison, Paul J., Gilmour, Gary, Bannerman, David M., Sanderson, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396315/
https://www.ncbi.nlm.nih.gov/pubmed/28186680
http://dx.doi.org/10.1111/ejn.13539
_version_ 1783230043350106112
author Boerner, Thomas
Bygrave, Alexei M.
Chen, Jingkai
Fernando, Anushka
Jackson, Stephanie
Barkus, Chris
Sprengel, Rolf
Seeburg, Peter H.
Harrison, Paul J.
Gilmour, Gary
Bannerman, David M.
Sanderson, David J.
author_facet Boerner, Thomas
Bygrave, Alexei M.
Chen, Jingkai
Fernando, Anushka
Jackson, Stephanie
Barkus, Chris
Sprengel, Rolf
Seeburg, Peter H.
Harrison, Paul J.
Gilmour, Gary
Bannerman, David M.
Sanderson, David J.
author_sort Boerner, Thomas
collection PubMed
description Group II metabotropic glutamate receptor agonists have been suggested as potential anti‐psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non‐competitive N‐methyl‐d‐aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome‐wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1 (−/−) mice during rewarded alternation performance in the T‐maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1 (−/−) mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non‐competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function.
format Online
Article
Text
id pubmed-5396315
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-53963152017-04-25 The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice Boerner, Thomas Bygrave, Alexei M. Chen, Jingkai Fernando, Anushka Jackson, Stephanie Barkus, Chris Sprengel, Rolf Seeburg, Peter H. Harrison, Paul J. Gilmour, Gary Bannerman, David M. Sanderson, David J. Eur J Neurosci Behavioural Neuroscience Group II metabotropic glutamate receptor agonists have been suggested as potential anti‐psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non‐competitive N‐methyl‐d‐aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome‐wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1 (−/−) mice during rewarded alternation performance in the T‐maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1 (−/−) mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non‐competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function. John Wiley and Sons Inc. 2017-03-04 2017-04 /pmc/articles/PMC5396315/ /pubmed/28186680 http://dx.doi.org/10.1111/ejn.13539 Text en © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Behavioural Neuroscience
Boerner, Thomas
Bygrave, Alexei M.
Chen, Jingkai
Fernando, Anushka
Jackson, Stephanie
Barkus, Chris
Sprengel, Rolf
Seeburg, Peter H.
Harrison, Paul J.
Gilmour, Gary
Bannerman, David M.
Sanderson, David J.
The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title_full The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title_fullStr The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title_full_unstemmed The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title_short The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice
title_sort group ii metabotropic glutamate receptor agonist ly354740 and the d2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in glua1 knockout mice
topic Behavioural Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396315/
https://www.ncbi.nlm.nih.gov/pubmed/28186680
http://dx.doi.org/10.1111/ejn.13539
work_keys_str_mv AT boernerthomas thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT bygravealexeim thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT chenjingkai thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT fernandoanushka thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT jacksonstephanie thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT barkuschris thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT sprengelrolf thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT seeburgpeterh thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT harrisonpaulj thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT gilmourgary thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT bannermandavidm thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT sandersondavidj thegroupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT boernerthomas groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT bygravealexeim groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT chenjingkai groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT fernandoanushka groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT jacksonstephanie groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT barkuschris groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT sprengelrolf groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT seeburgpeterh groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT harrisonpaulj groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT gilmourgary groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT bannermandavidm groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice
AT sandersondavidj groupiimetabotropicglutamatereceptoragonistly354740andthed2receptorantagonisthaloperidolreducelocomotorhyperactivitybutfailtorescuespatialworkingmemoryinglua1knockoutmice