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Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats.
Behav Brain Res. 2013 Nov 01; 256:520-8.BB

Abstract

Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD) are characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. Studies demonstrated rodent models of progesterone withdrawal (PWD) have a high level of constructive and descriptive validity to model hormonally-induced mood disorders in women. Here we evaluate the effects of several classes of antidepressants in PWD female Long-Evans rats using the forced swim test (FST) as a measure of antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A) receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days of administration, amitriptyline and vortioxetine significantly reduced immobility in the FST whereas fluoxetine and duloxetine were ineffective. After 3 injections over 48 h, neither fluoxetine nor duloxetine reduced immobility, whereas amitriptyline and vortioxetine significantly reduced FST immobility during PWD. When administered acutely during PWD, the 5-HT(1A) receptor agonist, flesinoxan, significantly reduced immobility, whereas the 5-HT(1A) receptor antagonist, WAY-100635, increased immobility. The 5-HT(3) receptor antagonist, ondansetron, significantly reduced immobility, whereas the 5-HT(3) receptor agonist, SR-57227, increased immobility. The 5-HT(7) receptor antagonist, SB-269970, was inactive, although the 5-HT(7) receptor agonist, AS-19, significantly increased PWD-induced immobility. None of the compounds investigated (ondansetron, flesinoxan and SB-269970) improved the effect of fluoxetine during PWD. These data indicate that modulation of specific 5-HT receptor subtypes is critical for manipulating FST immobility in this model of hormone-induced depression.

Authors+Show Affiliations

External Sourcing and Scientific Excellence, Lundbeck Research USA, United States. Electronic address: YLI@lundbeck.com.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24016840

Citation

Li, Yan, et al. "Serotonergic Receptor Mechanisms Underlying Antidepressant-like Action in the Progesterone Withdrawal Model of Hormonally Induced Depression in Rats." Behavioural Brain Research, vol. 256, 2013, pp. 520-8.
Li Y, Raaby KF, Sánchez C, et al. Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats. Behav Brain Res. 2013;256:520-8.
Li, Y., Raaby, K. F., Sánchez, C., & Gulinello, M. (2013). Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats. Behavioural Brain Research, 256, 520-8. https://doi.org/10.1016/j.bbr.2013.09.002
Li Y, et al. Serotonergic Receptor Mechanisms Underlying Antidepressant-like Action in the Progesterone Withdrawal Model of Hormonally Induced Depression in Rats. Behav Brain Res. 2013 Nov 1;256:520-8. PubMed PMID: 24016840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats. AU - Li,Yan, AU - Raaby,Kasper F, AU - Sánchez,Connie, AU - Gulinello,Maria, Y1 - 2013/09/07/ PY - 2013/05/11/received PY - 2013/08/27/revised PY - 2013/09/01/accepted PY - 2013/9/11/entrez PY - 2013/9/11/pubmed PY - 2014/6/27/medline KW - 5-HT KW - 8-OH-DPAT DPAT KW - 8-hydroxy-2-(di-N-propylamino)tetralin KW - AMI KW - ANOVA KW - AS KW - AS-19 KW - DLX KW - FLES KW - FLX KW - FST KW - Flesinoxan KW - Forced swim test KW - GABA KW - OND KW - Ondansetron KW - PMDD KW - PWD KW - Premenstrual dysphoric disorder (PMDD) KW - Progesterone withdrawal KW - SB KW - SB-269970 KW - SERT KW - SNRI KW - SR KW - SR-57227 KW - SSRI KW - VOR KW - Vortioxetine KW - WAY KW - WAY-100635 KW - amitriptyline KW - analysis of variance KW - duloxetine KW - flesinoxan KW - fluoxetine KW - forced swim test KW - ondansetron KW - premenstrual dysphoric disorder KW - progesterone withdrawal KW - selective serotonin reuptake inhibitor KW - serotonin KW - serotonin norepinephrine reuptake inhibitor KW - serotonin transporter KW - vortioxetine KW - γ-aminobutyric acid SP - 520 EP - 8 JF - Behavioural brain research JO - Behav. Brain Res. VL - 256 N2 - Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD) are characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. Studies demonstrated rodent models of progesterone withdrawal (PWD) have a high level of constructive and descriptive validity to model hormonally-induced mood disorders in women. Here we evaluate the effects of several classes of antidepressants in PWD female Long-Evans rats using the forced swim test (FST) as a measure of antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A) receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days of administration, amitriptyline and vortioxetine significantly reduced immobility in the FST whereas fluoxetine and duloxetine were ineffective. After 3 injections over 48 h, neither fluoxetine nor duloxetine reduced immobility, whereas amitriptyline and vortioxetine significantly reduced FST immobility during PWD. When administered acutely during PWD, the 5-HT(1A) receptor agonist, flesinoxan, significantly reduced immobility, whereas the 5-HT(1A) receptor antagonist, WAY-100635, increased immobility. The 5-HT(3) receptor antagonist, ondansetron, significantly reduced immobility, whereas the 5-HT(3) receptor agonist, SR-57227, increased immobility. The 5-HT(7) receptor antagonist, SB-269970, was inactive, although the 5-HT(7) receptor agonist, AS-19, significantly increased PWD-induced immobility. None of the compounds investigated (ondansetron, flesinoxan and SB-269970) improved the effect of fluoxetine during PWD. These data indicate that modulation of specific 5-HT receptor subtypes is critical for manipulating FST immobility in this model of hormone-induced depression. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/24016840/Serotonergic_receptor_mechanisms_underlying_antidepressant_like_action_in_the_progesterone_withdrawal_model_of_hormonally_induced_depression_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(13)00552-4 DB - PRIME DP - Unbound Medicine ER -