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Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats.
Behav Brain Res. 2021 04 23; 404:113159.BB

Abstract

Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5-HT1A receptor-mediated neurotransmission in the dorsal periaqueductal gray (dPAG), a key panic-associated area, has been implicated in the panicolytic effect of the selective serotonin reuptake inhibitor fluoxetine. However, it is still unknown whether this mechanism accounts for the antipanic effect of other classes of antidepressants drugs (ADs) and whether the 5-HT interaction with 5-HT2C receptors in this midbrain area (which increases anxiety) is implicated in the anxiogenic effect caused by short-term treatment with ADs. The results showed that previous injection of the 5-HT1A receptor antagonist WAY-100635 in the dPAG blocked the panicolytic-like effect caused by chronic systemic administration of the tricyclic AD imipramine in male Wistar rats tested in the elevated T-maze. Neither chronic treatment with imipramine nor fluoxetine changed the expression of 5-HT1A receptors in the dPAG. Treatment with these ADs also failed to significantly change ERK1/2 (extracellular-signal regulated kinase) phosphorylation level in this midbrain area. Blockade of 5-HT2C receptors in the dPAG with the 5-HT2C receptor antagonist SB-242084 did not change the anxiogenic effect caused by a single acute injection of fluoxetine or imipramine in the Vogel conflict test. These results reinforce the view that the facilitation of 5-HT1A receptor-mediated neurotransmission in the dPAG is a common mechanism involved in the panicolytic effect caused by chronic administration of ADs. On the other hand, the anxiogenic effect observed after short-term treatment with these drugs does not depend on 5-HT2C receptors located in the dPAG.

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Authors+Show Affiliations

Vilela-Costa HH

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Neuroscience Center - HILIFE, University of Helsinki, Finland.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Department of Health Sciences, Federal University of Espírito Santo (UFES), São Mateus, ES, Brazil.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil.

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil. Electronic address: zangross@fmrp.usp.br.

Pub Type(s)

Journal Article

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

Language

eng

PubMed ID

33571572

Citation

Vilela-Costa, Heloisa H., et al. "Role of 5-HT1A and 5-HT2C Receptors of the Dorsal Periaqueductal Gray in the Anxiety- and Panic-modulating Effects of Antidepressants in Rats." Behavioural Brain Research, vol. 404, 2021, p. 113159.

Vilela-Costa HH, Maraschin JC, Casarotto PC, et al. Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats. Behav Brain Res. 2021;404:113159.

Vilela-Costa, H. H., Maraschin, J. C., Casarotto, P. C., Sant'Ana, A. B., de Bortoli, V. C., Vicente, M. A., Campos, A. C., Guimarães, F. S., & Zangrossi, H. (2021). Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats. Behavioural Brain Research, 404, 113159. https://doi.org/10.1016/j.bbr.2021.113159

Vilela-Costa HH, et al. Role of 5-HT1A and 5-HT2C Receptors of the Dorsal Periaqueductal Gray in the Anxiety- and Panic-modulating Effects of Antidepressants in Rats. Behav Brain Res. 2021 04 23;404:113159. PubMed PMID: 33571572.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats. AU - Vilela-Costa,Heloisa H, AU - Maraschin,Jhonatan Christian, AU - Casarotto,Plinio C, AU - Sant'Ana,Ana Beatriz, AU - de Bortoli,Valquiria C, AU - Vicente,Maria Adrielle, AU - Campos,Alline Cristina, AU - Guimarães,Francisco S, AU - Zangrossi,Helio,Jr Y1 - 2021/02/08/ PY - 2020/11/26/received PY - 2021/01/27/revised PY - 2021/01/31/accepted PY - 2021/2/12/pubmed PY - 2022/1/21/medline PY - 2021/2/11/entrez KW - Anxiety KW - Dorsal periaqueductal gray KW - Fluoxetine KW - Imipramine KW - Panic KW - Serotonin SP - 113159 EP - 113159 JF - Behavioural brain research JO - Behav Brain Res VL - 404 N2 - Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5-HT1A receptor-mediated neurotransmission in the dorsal periaqueductal gray (dPAG), a key panic-associated area, has been implicated in the panicolytic effect of the selective serotonin reuptake inhibitor fluoxetine. However, it is still unknown whether this mechanism accounts for the antipanic effect of other classes of antidepressants drugs (ADs) and whether the 5-HT interaction with 5-HT2C receptors in this midbrain area (which increases anxiety) is implicated in the anxiogenic effect caused by short-term treatment with ADs. The results showed that previous injection of the 5-HT1A receptor antagonist WAY-100635 in the dPAG blocked the panicolytic-like effect caused by chronic systemic administration of the tricyclic AD imipramine in male Wistar rats tested in the elevated T-maze. Neither chronic treatment with imipramine nor fluoxetine changed the expression of 5-HT1A receptors in the dPAG. Treatment with these ADs also failed to significantly change ERK1/2 (extracellular-signal regulated kinase) phosphorylation level in this midbrain area. Blockade of 5-HT2C receptors in the dPAG with the 5-HT2C receptor antagonist SB-242084 did not change the anxiogenic effect caused by a single acute injection of fluoxetine or imipramine in the Vogel conflict test. These results reinforce the view that the facilitation of 5-HT1A receptor-mediated neurotransmission in the dPAG is a common mechanism involved in the panicolytic effect caused by chronic administration of ADs. On the other hand, the anxiogenic effect observed after short-term treatment with these drugs does not depend on 5-HT2C receptors located in the dPAG. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/33571572/Role_of_5_HT1A_and_5_HT2C_receptors_of_the_dorsal_periaqueductal_gray_in_the_anxiety__and_panic_modulating_effects_of_antidepressants_in_rats_ DB - PRIME DP - Unbound Medicine ER -