Evidence map›Paper›PMID 31960362›Full record

ArticleMolecular neurobiology2020

Comparative Pro-cognitive and Neurochemical Profiles of Glycine Modulatory Site Agonists and Glycine Reuptake Inhibitors in the Rat: Potential Relevance to Cognitive Dysfunction and Its Management.

Kevin C F Fone, David J G Watson, Rodolphe I Billiras, Dorothee I Sicard, Anne Dekeyne, Jean-Michel Rivet, Alain Gobert, Mark J Millan

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments.International journal of molecular sciences · 2021
    Review
  5. Article
  6. Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist d-serine.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  7. Review
  8. Article
  9. Article
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Kevin C F FoneSchool of Life Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham, NG7 2UH, UK. kevin.fone@nottingham.ac.uk.ORCID https://orcid.org/0000-0001-8760-2167
David J G WatsonSchool of Life Sciences, Queen's Medical Centre, The University of Nottingham, Nottingham, NG7 2UH, UK.
Rodolphe I BillirasCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France.
Dorothee I SicardCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France.
Anne DekeyneCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France.
Jean-Michel RivetCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France.
Alain GobertCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France.
Mark J MillanCentre for Therapeutic Innovation-CNS, Institut de Recherche Servier, Centre de Recherches de Croissy, 125 Chemin de Ronde, 78290, Croissy-sur-Seine, France. mark.millan@servier.com.
University of Nottingham · GBAVL (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Frontocortical NMDA receptors are pivotal in regulating cognition and mood, are hypofunctional in schizophrenia, and may contribute to autistic spectrum disorders. Despite extensive interest in agents potentiating activity at the co-agonist glycine modulatory site, few comparative functional studies exist. This study systematically compared the actions of the glycine reuptake inhibitors, sarcosine (40-200 mg/kg) and ORG24598 (0.63-5 mg/kg), the agonists, glycine (40-800 mg/kg), and D-serine (10-160 mg/kg) and the partial agonists, S18841 (2.5 mg/kg s.c.) and D-cycloserine (2.5-40 mg/kg) that all dose-dependently prevented scopolamine disruption of social recognition in adult rats. Over similar dose ranges, they also prevented a delay-induced impairment of novel object recognition (NOR). Glycine reuptake inhibitors specifically elevated glycine but not D-serine levels in rat prefrontal cortical (PFC) microdialysates, while glycine and D-serine markedly increased levels of glycine and D-serine, respectively. D-Cycloserine slightly elevated D-serine levels. Conversely, S18841 exerted no influence on glycine, D-serine, other amino acids, monamines, or acetylcholine. Reversal of NOR deficits by systemic S18841 was prevented by the NMDA receptor antagonist, CPP (20 mg/kg), and the glycine modulatory site antagonist, L701,324 (10 mg/kg). S18841 blocked deficits in NOR following microinjection into the PFC (2.5-10 μg/side) but not the striatum. Finally, in rats socially isolated from weaning (a neurodevelopmental model of schizophrenia), S18841 (2.5 and 10 mg/kg s.c.) reversed impairment of NOR and contextual fear-motivated learning without altering isolation-induced hyperactivity. In conclusion, despite contrasting neurochemical profiles, partial glycine site agonists and glycine reuptake inhibitors exhibit comparable pro-cognitive effects in rats of potential relevance to treatment of schizophrenia and other brain disorders where cognitive performance is impaired.

Indexed as

Amino AcidsAnimalsAutism Spectrum DisorderCognitionCognition DisordersCycloserineDose-Response Relationship, DrugFreezing Reaction, CatalepticGlycineGlycine AgentsMaleMemory, Short-TermMotor ActivityNeurotransmitter Uptake InhibitorsNootropic AgentsPrefrontal CortexAmino AcidsCycloserineGlycineGlycine AgentsNeurotransmitter Uptake InhibitorsNootropic Agentsorg 24598Receptors, GlycineReceptors, N-Methyl-D-AspartateSarcosineScopolamineSerineCognitionD-serineGlycine modulatory siteMicrodialysisNMDA receptorPrefrontal cortexSchizophreniaSocial cognition

Identifiers

PMID31960362
PMCPMC7170834
OpenAlexW3002475213

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.