Connie Sánchez

Vortioxetine treatment reverses subchronic PCP treatment-induced cognitive impairments: A potential role for serotonin receptor-mediated regulation of GABA neurotransmission

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Vortioxetine treatment reverses subchronic PCP treatment-induced cognitive impairments : A potential role for serotonin receptor-mediated regulation of GABA neurotransmission. / Pehrson, Alan L.; Pedersen, Christian S.; Tølbøl, Kirstine Sloth; Sanchez, Connie.

In: Frontiers in Pharmacology, Vol. 9, No. MAR, 162, 06.03.2018.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Pehrson, Alan L. ; Pedersen, Christian S. ; Tølbøl, Kirstine Sloth ; Sanchez, Connie. / Vortioxetine treatment reverses subchronic PCP treatment-induced cognitive impairments : A potential role for serotonin receptor-mediated regulation of GABA neurotransmission. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. MAR.

Bibtex

@article{ceaf3a1b6c6345b982179fe86250ccca,
title = "Vortioxetine treatment reverses subchronic PCP treatment-induced cognitive impairments: A potential role for serotonin receptor-mediated regulation of GABA neurotransmission",
abstract = " Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission. In this paper, we attempt to bridge this gap by evaluating vortioxetine's effects in the subchronic PCP (subPCP) model, which induces impaired cognitive function and altered GABA and glutamate neurotransmission. We demonstrate that acute or subchronic vortioxetine treatment attenuated subPCP-induced deficits in attentional set shifting (AST) performance, and that the selective 5-HT 3 receptor antagonist ondansetron or the 5-HT reuptake inhibitor escitalopram could mimic this effect. Furthermore, acute vortioxetine treatment reversed subPCP-induced object recognition (OR) deficits in rats, while subchronic vortioxetine reversed subPCP-induced Object Recognition and object placement impairments in mice. Finally, subPCP treatment reduced GABA B receptor expression in a manner that was insensitive to vortioxetine treatment, and subchronic vortioxetine treatment alone, but not in combination with subPCP, significantly increased GABA's affinity for the GABA A receptor. These data suggest that vortioxetine reverses cognitive impairments in a model associated with altered GABA and glutamate neurotransmission, further supporting the hypothesis that vortioxetine's GABAergic and glutamatergic effects are relevant for cognitive function. ",
keywords = "Attentional set-shifting test, GABA, Novel object placement, Novel object recognition, Serotonin, Subchronic PCP, Vortioxetine",
author = "Pehrson, {Alan L.} and Pedersen, {Christian S.} and T{\o}lb{\o}l, {Kirstine Sloth} and Connie Sanchez",
year = "2018",
month = mar,
day = "6",
doi = "10.3389/fphar.2018.00162",
language = "English",
volume = "9",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Research Foundation",
number = "MAR",

}

RIS

TY - JOUR

T1 - Vortioxetine treatment reverses subchronic PCP treatment-induced cognitive impairments

T2 - A potential role for serotonin receptor-mediated regulation of GABA neurotransmission

AU - Pehrson, Alan L.

AU - Pedersen, Christian S.

AU - Tølbøl, Kirstine Sloth

AU - Sanchez, Connie

PY - 2018/3/6

Y1 - 2018/3/6

N2 - Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission. In this paper, we attempt to bridge this gap by evaluating vortioxetine's effects in the subchronic PCP (subPCP) model, which induces impaired cognitive function and altered GABA and glutamate neurotransmission. We demonstrate that acute or subchronic vortioxetine treatment attenuated subPCP-induced deficits in attentional set shifting (AST) performance, and that the selective 5-HT 3 receptor antagonist ondansetron or the 5-HT reuptake inhibitor escitalopram could mimic this effect. Furthermore, acute vortioxetine treatment reversed subPCP-induced object recognition (OR) deficits in rats, while subchronic vortioxetine reversed subPCP-induced Object Recognition and object placement impairments in mice. Finally, subPCP treatment reduced GABA B receptor expression in a manner that was insensitive to vortioxetine treatment, and subchronic vortioxetine treatment alone, but not in combination with subPCP, significantly increased GABA's affinity for the GABA A receptor. These data suggest that vortioxetine reverses cognitive impairments in a model associated with altered GABA and glutamate neurotransmission, further supporting the hypothesis that vortioxetine's GABAergic and glutamatergic effects are relevant for cognitive function.

AB - Major depressive disorder (MDD) is associated with cognitive impairments that may contribute to poor functional outcomes. Clinical data suggests that the multimodal antidepressant vortioxetine attenuates some cognitive impairments in MDD patients, but the mechanistic basis for these improvements is unclear. One theory suggests that vortioxetine improves cognition by suppressing γ-amino butyric acid (GABA)ergic neurotransmission, thereby increasing glutamatergic activation. Vortioxetine's effects on cognition, GABA and glutamate neurotransmission have been supported in separate experiments, but no empirical work has directly connected vortioxetine's cognitive effects to those on GABA and glutamate neurotransmission. In this paper, we attempt to bridge this gap by evaluating vortioxetine's effects in the subchronic PCP (subPCP) model, which induces impaired cognitive function and altered GABA and glutamate neurotransmission. We demonstrate that acute or subchronic vortioxetine treatment attenuated subPCP-induced deficits in attentional set shifting (AST) performance, and that the selective 5-HT 3 receptor antagonist ondansetron or the 5-HT reuptake inhibitor escitalopram could mimic this effect. Furthermore, acute vortioxetine treatment reversed subPCP-induced object recognition (OR) deficits in rats, while subchronic vortioxetine reversed subPCP-induced Object Recognition and object placement impairments in mice. Finally, subPCP treatment reduced GABA B receptor expression in a manner that was insensitive to vortioxetine treatment, and subchronic vortioxetine treatment alone, but not in combination with subPCP, significantly increased GABA's affinity for the GABA A receptor. These data suggest that vortioxetine reverses cognitive impairments in a model associated with altered GABA and glutamate neurotransmission, further supporting the hypothesis that vortioxetine's GABAergic and glutamatergic effects are relevant for cognitive function.

KW - Attentional set-shifting test

KW - GABA

KW - Novel object placement

KW - Novel object recognition

KW - Serotonin

KW - Subchronic PCP

KW - Vortioxetine

UR - http://www.scopus.com/inward/record.url?scp=85043343956&partnerID=8YFLogxK

U2 - 10.3389/fphar.2018.00162

DO - 10.3389/fphar.2018.00162

M3 - Journal article

C2 - 29559911

AN - SCOPUS:85043343956

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - MAR

M1 - 162

ER -