ArticlePsychopharmacology2013
Subchronic memantine induced concurrent functional disconnectivity and altered ultra-structural tissue integrity in the rodent brain: revealed by multimodal MRI.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 21 citations in OpenAlex.
- Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior.Psychopharmacology · 2022Article
- Pharmacological interrogation of TrkA-mediated mechanisms in hippocampal-dependent memory consolidation.PloS one · 2019Article
- Studies on a novel regimen for management of orofacial pain and morphine tolerance.Journal of dental sciences · 2018Article
- A Role for Prefrontal Cortical NMDA Receptors in Murine Alcohol-Heightened Aggression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Dynamic Causal Modeling of Preclinical Autosomal-Dominant Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2018Article
- Biomarkers, designs, and interpretations of resting-state fMRI in translational pharmacological research: A review of state-of-the-Art, challenges, and opportunities for studying brain chemistry.Human brain mapping · 2017Review
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAn effective NMDA antagonist imaging model may find key utility in advancing schizophrenia drug discovery research. We investigated effects of subchronic treatment with the NMDA antagonist memantine by using behavioural observation and multimodal MRI.
methodsPharmacological MRI (phMRI) was used to map the neuroanatomical binding sites of memantine after acute and subchronic treatment. Resting state fMRI (rs-fMRI) and diffusion MRI were used to study the changes in functional connectivity (FC) and ultra-structural tissue integrity before and after subchronic memantine treatment. Further corroborating behavioural evidences were documented.
resultsDose-dependent phMRI activation was observed in the prelimbic cortex following acute doses of memantine. Subchronic treatment revealed significant effects in the hippocampus, cingulate, prelimbic and retrosplenial cortices. Decreases in FC amongst the hippocampal and frontal cortical structures (prelimbic, cingulate) were apparent through rs-fMRI investigation, indicating a loss of connectivity. Diffusion kurtosis MRI showed decreases in fractional anisotropy and mean diffusivity changes, suggesting ultra-structural changes in the hippocampus and cingulate cortex. Limited behavioural assessment suggested that memantine induced behavioural effects comparable to other NMDA antagonists as measured by locomotor hyperactivity and that the effects could be reversed by antipsychotic drugs.
conclusionOur findings substantiate the hypothesis that repeated NMDA receptor blockade with nonspecific, noncompetitive NMDA antagonists may lead to functional and ultra-structural alterations, particularly in the hippocampus and cingulate cortex. These changes may underlie the behavioural effects. Furthermore, the present findings underscore the utility and the translational potential of multimodal MR imaging and acute/subchronic memantine model in the search for novel disease-modifying treatments for schizophrenia.
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