Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: a preliminary investigation
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RATIONALE: Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). METHODS: Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. RESULTS: Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed. CONCLUSIONS: These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.
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DA levels are elevated in the mPFC during the test trial of NOP memory in rats.
“In addition, DA levels were found to be elevated in the mPFC during the test trial of NOP memory in rats (McLean et al., 2017).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as McLean et al., 2017
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Chao, O. Y., de Souza Silva, M. A., Yang, Y.-M., & Huston, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.007 · Cited by 158 · see citing works
- Authors
- McLean, S. L., Harte, M. K., Neill, J. C., & Young, A. M.
- Affiliations
- University of Bradford (GB)
- University of Manchester (GB)
- University of Leicester (GB)
- Corresponding author
- McLean, Samantha L
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2017-04-26
- Volume
- 31
- Issue
- 6
- Pages
- 660-666
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2608116068
- Cited by
- 16
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 1
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Bradford Scholars (University of Bradford) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Funders
- University of Leicester
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine dysregulation, prefrontal cortex, schizophrenia, cognitive impairment, novel object recognition, in vivo microdialysis, animal models of schizophrenia, Lister hooded rats, dopamine release
- MeSH terms
- Animals, Behavior, Animal, Cognition, Disease Models, Animal, Dopamine, Female, Phencyclidine, Schizophrenia, Prefrontal Cortex, Recognition, Psychology, Rats, Cognitive Dysfunction
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