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D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI

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Santini, Martin A ; Balu, Darrick T ; Puhl, Matthew D ; Hill-Smith, Tiffany E ; Berg, Alexandra R ; Lucki, Irwin ; Mikkelsen, Jens D ; Coyle, Joseph T. / D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI. I: Behavioural Brain Research. 2014 ; Bind 259. s. 242-46.

Bibtex

@article{0dbabc5802944ecaa8e579b2cb4d92de,
title = "D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI",
abstract = "Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction, a serine racemase knockout (SRKO) mouse, to explore the role of glutamatergic transmission in regulating the 5-HT2AR-mediated cellular and behavioral responses. SRKO mice treated with the 5-HT2AR agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished HTR and lower induction of c-fos mRNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation.",
author = "Santini, {Martin A} and Balu, {Darrick T} and Puhl, {Matthew D} and Hill-Smith, {Tiffany E} and Berg, {Alexandra R} and Irwin Lucki and Mikkelsen, {Jens D} and Coyle, {Joseph T}",
note = "Copyright {\circledC} 2013. Published by Elsevier B.V.",
year = "2014",
doi = "10.1016/j.bbr.2013.11.022",
language = "English",
volume = "259",
pages = "242--46",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI

AU - Santini, Martin A

AU - Balu, Darrick T

AU - Puhl, Matthew D

AU - Hill-Smith, Tiffany E

AU - Berg, Alexandra R

AU - Lucki, Irwin

AU - Mikkelsen, Jens D

AU - Coyle, Joseph T

N1 - Copyright © 2013. Published by Elsevier B.V.

PY - 2014

Y1 - 2014

N2 - Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction, a serine racemase knockout (SRKO) mouse, to explore the role of glutamatergic transmission in regulating the 5-HT2AR-mediated cellular and behavioral responses. SRKO mice treated with the 5-HT2AR agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished HTR and lower induction of c-fos mRNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation.

AB - Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction, a serine racemase knockout (SRKO) mouse, to explore the role of glutamatergic transmission in regulating the 5-HT2AR-mediated cellular and behavioral responses. SRKO mice treated with the 5-HT2AR agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished HTR and lower induction of c-fos mRNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation.

U2 - 10.1016/j.bbr.2013.11.022

DO - 10.1016/j.bbr.2013.11.022

M3 - Journal article

VL - 259

SP - 242

EP - 246

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -

ID: 41499618