Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action

Research output: Contribution to journalJournal articleResearchpeer-review

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Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action. / Fitzpatrick, Ciarán Martin; Larsen, Maria; Madsen, Louise; Pickering, Darryl S; Clausen, Rasmus Prætorius; Andreasen T., Jesper.

In: Behavioural Pharmacology, Vol. 27, No. 6, 26.06.2016, p. 549-555.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Fitzpatrick, CM, Larsen, M, Madsen, L, Pickering, DS, Clausen, RP & Andreasen T., J 2016, 'Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action', Behavioural Pharmacology, vol. 27, no. 6, pp. 549-555. https://doi.org/10.1097/FBP.0000000000000243

APA

Fitzpatrick, C. M., Larsen, M., Madsen, L., Pickering, D. S., Clausen, R. P., & Andreasen T., J. (2016). Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action. Behavioural Pharmacology, 27(6), 549-555. https://doi.org/10.1097/FBP.0000000000000243

Vancouver

Fitzpatrick CM, Larsen M, Madsen L, Pickering DS, Clausen RP, Andreasen T. J. Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action. Behavioural Pharmacology. 2016 Jun 26;27(6):549-555. https://doi.org/10.1097/FBP.0000000000000243

Author

Fitzpatrick, Ciarán Martin ; Larsen, Maria ; Madsen, Louise ; Pickering, Darryl S ; Clausen, Rasmus Prætorius ; Andreasen T., Jesper. / Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action. In: Behavioural Pharmacology. 2016 ; Vol. 27, No. 6. pp. 549-555.

Bibtex

@article{5633e1a8083640e087cd8a63135ab876,
title = "Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action",
abstract = "Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR).Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission, and AMPAR positive allosteric modulators (APAMs) have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor (SSRI) citalopram (0-10 mg/kg) was investigated in mice, using the APAM LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed with the forced swim test (FST), while anxiolytic-like effects were tested with the elevated zero maze (EZM) and the marble burying test (MBT). LY451646 (3 mg/kg) increased swim distance in the FST and a sub-active dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the MBT, LY451646 (3 mg/kg) showed no effect alone but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression, as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments.",
author = "Fitzpatrick, {Ciar{\'a}n Martin} and Maria Larsen and Louise Madsen and Pickering, {Darryl S} and Clausen, {Rasmus Pr{\ae}torius} and {Andreasen T.}, Jesper",
year = "2016",
month = "6",
day = "26",
doi = "10.1097/FBP.0000000000000243",
language = "English",
volume = "27",
pages = "549--555",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams & Wilkins",
number = "6",

}

RIS

TY - JOUR

T1 - Positive allosteric modulation of AMPA receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action

AU - Fitzpatrick, Ciarán Martin

AU - Larsen, Maria

AU - Madsen, Louise

AU - Pickering, Darryl S

AU - Clausen, Rasmus Prætorius

AU - Andreasen T., Jesper

PY - 2016/6/26

Y1 - 2016/6/26

N2 - Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR).Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission, and AMPAR positive allosteric modulators (APAMs) have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor (SSRI) citalopram (0-10 mg/kg) was investigated in mice, using the APAM LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed with the forced swim test (FST), while anxiolytic-like effects were tested with the elevated zero maze (EZM) and the marble burying test (MBT). LY451646 (3 mg/kg) increased swim distance in the FST and a sub-active dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the MBT, LY451646 (3 mg/kg) showed no effect alone but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression, as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments.

AB - Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR).Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission, and AMPAR positive allosteric modulators (APAMs) have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor (SSRI) citalopram (0-10 mg/kg) was investigated in mice, using the APAM LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed with the forced swim test (FST), while anxiolytic-like effects were tested with the elevated zero maze (EZM) and the marble burying test (MBT). LY451646 (3 mg/kg) increased swim distance in the FST and a sub-active dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the MBT, LY451646 (3 mg/kg) showed no effect alone but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression, as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments.

U2 - 10.1097/FBP.0000000000000243

DO - 10.1097/FBP.0000000000000243

M3 - Journal article

C2 - 27341500

VL - 27

SP - 549

EP - 555

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

IS - 6

ER -

ID: 152964628