ArticlePsychopharmacology2005
The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: a comparison.
Article in Psychopharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 111 citations in OpenAlex.
- Trial
- Preclinical pharmacology of alogabat: a novel GABAFrontiers in pharmacology · 2025Article
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- Article
- Sex differences and hormonal regulation of metabotropic glutamate receptor synaptic plasticity.International review of neurobiology · 2023Review
- Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission.International journal of molecular sciences · 2022Review
- Basmisanil, a highly selective GABAScientific reports · 2021Article
- mGlu5 in GABAergic neurons modulates spontaneous and psychostimulant-induced locomotor activity.Psychopharmacology · 2020Article
- Glutamate Systems in DSM-5 Anxiety Disorders: Their Role and a Review of Glutamate and GABA Psychopharmacology.Frontiers in psychiatry · 2020Review
- In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Touchscreen testing reveals clinically relevant cognitive abnormalities in a mouse model of schizophrenia lacking metabotropic glutamate receptor 5.Scientific reports · 2018Article
- Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Amygdalar activation of group I metabotropic glutamate receptors produces anti- and pro-conflict effects depending upon animal sex in a sexually dimorphic conditioned conflict-based anxiety model.Behavioural brain research · 2016Article
- Partial mGlu₅ Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Spatial Learning Requires mGlu5 Signalling in the Dorsal Hippocampus.Neurochemical research · 2015Article
- Dose-dependent, saturable occupancy of the metabotropic glutamate subtype 5 receptor by fenobam as measured with [Synapse (New York, N.Y.) · 2014Article
- Interaction between the mGlu receptors 5 antagonist, MPEP, and amphetamine on memory and motor functions in mice.Psychopharmacology · 2013Article
- mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion.PloS one · 2013Article
- Translational animal models of autism and neurodevelopmental disorders.Dialogues in clinical neuroscience · 2012Review
- Differential effects of diazepam and MPEP on habituation and neuro-behavioural processes in inbred mice.Behavioral and brain functions : BBF · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleAntagonists at the metabotropic glutamate 5 (mGlu5) receptor produce robust anxiolytic effects in a number of rat tests. However, there is evidence that mGlu5 receptor antagonists may also impair working memory and spatial learning following intracerebroventricular administration.
objectivesThe aim of this study is to compare the effect of the potent and selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-piperidine (MPEP), administered systemically on rodent tests of cognition and anxiety.
methodsMPEP was assessed in the following rodent tests, 60 min following oral administration: Geller--Seifter conflict, conditioned emotional response (CER), Vogel conflict, delayed match to position (DMTP) and Morris water maze. Diazepam was also tested as a comparator.
resultsMPEP had a significant anxiolytic effect, comparable in magnitude to diazepam, at 10--30 mg/kg in the two conflict and CER tasks. There was no effect of MPEP up to 30 mg/kg on working memory in the DMTP task, but at 100 mg/kg, there was a significant reduction in choice accuracy at the longest delay interval (24 s). MPEP (3--30 mg/kg) did not significantly impair spatial learning in the Morris water maze, although during the last probe trial, 30-mg/kg-treated rats were significantly less accurate than controls. In contrast, diazepam significantly impaired performance in both the DMTP and Morris water maze tests. Assessment of plasma and brain concentration of MPEP approximately 75 min following oral administration showed a dose linearity from 3 to 30 mg/kg and good brain penetration, i.e. a brain/plasma ratio of 3.1.
conclusionsOral administration of the selective mGlu5 receptor antagonist MPEP induces a robust anxiolytic-like effect in rat conflict tests comparable to that seen with diazepam, but in contrast to diazepam, MPEP does not impair working memory or spatial learning at anxiolytic doses.
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