Translating the MAM model of psychosis to humans
Open accessAbstract
Elevated dopamine function and alterations in medial temporal lobe (MTL) structure and function are two of the most robust findings in schizophrenia, but how interactions between these abnormalities underlie the onset of psychosis is unclear. The methylazoxymethanol acetate (MAM) rodent model proposes that psychosis develops as a result of a perturbation of MTL function, leading to elevated striatal dopamine dysfunction. Here, we review several recent neuroimaging studies that examine components of the putative model in humans with an ultra high risk (UHR) of the psychosis. While data from these studies are broadly consistent with the MAM model, caution is required when comparing data across animal and human studies.
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Both MAM and NVHL models reproduce some of the defects observed in schizophrenia, including functional deficits in PV+ fast spiking interneurons.
“Both models reproduce some of the defects observed in schizophrenia, including functional deficits in PV+ fast spiking interneurons.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [56]
These models are primarily based on pharmacological lesions of the developing hippocampus, such as the prenatal exposure to MAM and the NVHL models.
“These are primarily based on pharmacological lesions of the developing hippocampus, such as the prenatal exposure to methylazoxymethanol acetate (MAM) and the neonatal ventral hippocampal lesion (NVHL) models 55,56 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [56]
Changes in dopaminergic neurons might be secondary to the disruption of cortical circuits in the MAM model.
“and studies in the MAM model have shown that the changes in dopaminergic neurons might be secondary to the disruption of cortical circuits 56 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [56]
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References 140 · Cited by 165
- Authors
- Modinos, G., Allen, P., Grace, A. A., & McGuire, P.
- Affiliations
- King's College London (GB)
- University of Pittsburgh (US)
- Corresponding author
- Modinos, Gemma
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 38
- Issue
- 3
- Pages
- 129-138
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC4455929
- OpenAlex
- W2035872682
- Cited by
- 165
- References
- 140
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 22 · 2021: 16 · 2020: 15 · 2019: 19 · 2018: 16 · 2017: 16 · 2016: 17 · 2015: 4
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust (091667)
- National Institutes of Health (2r01mh057440-26a1)
- National Institute of Mental Health (R01-MH057440, R37MH057440)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Keywords
- psychosis, schizophrenia, clinical high risk for psychosis, medial temporal lobe, dopamine, animal-to-human translation, transition to psychosis
- MeSH terms
- Animals, Brain, Disease Models, Animal, Humans, Methylazoxymethanol Acetate, Psychotic Disorders
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