Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application

Julia C. Bartsch; Pawel Fidzinski; Jojanneke H. Huck; Heide Hörtnagl; Richard Kovács; Agustin Liotta; Josef Priller; Christian Wozny; Joachim Behr

doi:10.1038/npp.2014.276

Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application

Julia C. Bartsch, Pawel Fidzinski, Jojanneke H. Huck, Heide Hörtnagl, Richard Kovács, Agustin Liotta, Josef Priller, Christian Wozny, Joachim Behr

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca 2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.

Original language	English
Pages (from-to)	987-995
Number of pages	9
Journal	Neuropsychopharmacology
Volume	40
Issue number	4
DOIs	https://doi.org/10.1038/npp.2014.276
State	Published - Mar 2015
Externally published	Yes

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@article{398caea711224c3093807cfb28f615ea,

title = "Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application",

abstract = "Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca 2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.",

author = "Bartsch, {Julia C.} and Pawel Fidzinski and Huck, {Jojanneke H.} and Heide H{\"o}rtnagl and Richard Kov{\'a}cs and Agustin Liotta and Josef Priller and Christian Wozny and Joachim Behr",

note = "Funding Information: This work was supported by German Research Foundation (DFG) grants to JB (BE 2011/6-1), RK (KO3814/1-1), and JCB (GRK 1123). Professor Behr has received compensation as a member of the scientific advisory board of Roche. The authors declare no conflict of interest.",

year = "2015",

month = mar,

doi = "10.1038/npp.2014.276",

language = "English",

volume = "40",

pages = "987--995",

journal = "Neuropsychopharmacology",

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T1 - Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application

AU - Bartsch, Julia C.

AU - Fidzinski, Pawel

AU - Huck, Jojanneke H.

AU - Hörtnagl, Heide

AU - Kovács, Richard

AU - Liotta, Agustin

AU - Priller, Josef

AU - Wozny, Christian

AU - Behr, Joachim

N1 - Funding Information: This work was supported by German Research Foundation (DFG) grants to JB (BE 2011/6-1), RK (KO3814/1-1), and JCB (GRK 1123). Professor Behr has received compensation as a member of the scientific advisory board of Roche. The authors declare no conflict of interest.

PY - 2015/3

Y1 - 2015/3

N2 - Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca 2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.

AB - Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca 2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.

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JO - Neuropsychopharmacology

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Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application

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