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dc.contributor.author
Nakao, Kazuhito
dc.contributor.author
Jeevakumar, Vivek
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Jiang, Sunny Zhihong
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Fujita, Yuko
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Diaz, Noelia Belen
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Pretell Annan, Carlos Alfredo
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Eskow Jaunarajs, Karen L.
dc.contributor.author
Hashimoto, Kenji
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Belforte, Juan Emilio
dc.contributor.author
Nakazawa, Kazu
dc.date.available
2020-12-16T15:28:32Z
dc.date.issued
2019-01
dc.identifier.citation
Nakao, Kazuhito; Jeevakumar, Vivek; Jiang, Sunny Zhihong; Fujita, Yuko; Diaz, Noelia Belen; et al.; Schizophrenia-like dopamine release abnormalities in a mouse model of NMDA receptor hypofunction; Oxford University Press; Schizophrenia Bulletin; 45; 1; 1-2019; 138-147
dc.identifier.issn
0586-7614
dc.identifier.uri
http://hdl.handle.net/11336/120570
dc.description.abstract
Amphetamine-induced augmentation of striatal dopamine and its blunted release in prefrontal cortex (PFC) is a hallmark of schizophrenia pathophysiology. Although N-methyl-D-aspartate receptor (NMDAR) hypofunction is also implicated in schizophrenia, it remains unclear whether NMDAR hypofunction leads to dopamine release abnormalities. We previously demonstrated schizophrenialike phenotypes in GABAergic neuron-specific NMDAR hypofunctional mutant mice, in which Ppp1r2-Cre dependent deletion of indispensable NMDAR channel subunit Grin1 is induced in corticolimbic GABAergic neurons including parvalbumin (PV)-positive neurons, in postnatal development, but not in adulthood. Here, we report enhanced dopaminomimetic-induced locomotor activity in these mutants, along with bidirectional, site-specific changes in in vivo amphetamine-induced dopamine release: nucleus accumbens (NAc) dopamine release was enhanced by amphetamine in postnatal Ppp1r2-Cre/Grin1 knockout (KO) mice, whereas dopamine release was dramatically reduced in the medial PFC (mPFC) compared to controls. Basal tissue dopamine levels in both the NAc and mPFC were unaffected. Interestingly, the magnitude and distribution of amphetamine-induced c-Fos expression in dopamine neurons was comparable between genotypes across dopaminergic input subregions in the ventral tegmental area (VTA). These effects appear to be both developmentally and cell-type specifically modulated, since PV-specific Grin1 KO mice could induce the same effects as seen in postnatal-onset Ppp1r2-Cre/Grin1 KO mice, but no such abnormalities were observed in somatostatinCre/Grin1 KO mice or adult-onset Ppp1r2-Cre/Grin1 KO mice. These results suggest that PV GABAergic neuronNMDAR hypofunction in postnatal development confers bidirectional NAc hyper- and mPFC hypo-sensitivity to amphetamine-induced dopamine release, similar to that classically observed in schizophrenia pathophysiology.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AMPHETAMINE
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GABAERGIC NEURONS
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MICRODIALYSIS
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PARVALBUMIN
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PREFRO NTAL CORTEX
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STRIATUM
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Schizophrenia-like dopamine release abnormalities in a mouse model of NMDA receptor hypofunction
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-19T21:39:06Z
dc.journal.volume
45
dc.journal.number
1
dc.journal.pagination
138-147
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Nakao, Kazuhito. University Of Alabama At Birmingham; Estados Unidos
dc.description.fil
Fil: Jeevakumar, Vivek. University Of Alabama At Birmingham; Estados Unidos
dc.description.fil
Fil: Jiang, Sunny Zhihong. University Of Alabama At Birmingham; Estados Unidos
dc.description.fil
Fil: Fujita, Yuko. No especifíca;
dc.description.fil
Fil: Diaz, Noelia Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Pretell Annan, Carlos Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Eskow Jaunarajs, Karen L.. University Of Alabama At Birmingham; Estados Unidos
dc.description.fil
Fil: Hashimoto, Kenji. Chiba University; Japón
dc.description.fil
Fil: Belforte, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Nakazawa, Kazu. University Of Alabama At Birmingham; Estados Unidos
dc.journal.title
Schizophrenia Bulletin
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/schbul/sby003
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/schizophreniabulletin/article/45/1/138/4832735
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