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Opposing roles for cannabinoid receptor type-1 (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats.
Neuropsychopharmacology. 2012 Jan; 37(2):478-86.N

Abstract

The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety- and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB₁ and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB₁-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB₁-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB₁ and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB₁ receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21937980

Citation

Casarotto, Plínio C., et al. "Opposing Roles for Cannabinoid Receptor Type-1 (CB₁) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) On the Modulation of Panic-like Responses in Rats." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 37, no. 2, 2012, pp. 478-86.
Casarotto PC, Terzian AL, Aguiar DC, et al. Opposing roles for cannabinoid receptor type-1 (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology. 2012;37(2):478-86.
Casarotto, P. C., Terzian, A. L., Aguiar, D. C., Zangrossi, H., Guimarães, F. S., Wotjak, C. T., & Moreira, F. A. (2012). Opposing roles for cannabinoid receptor type-1 (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(2), 478-86. https://doi.org/10.1038/npp.2011.207
Casarotto PC, et al. Opposing Roles for Cannabinoid Receptor Type-1 (CB₁) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) On the Modulation of Panic-like Responses in Rats. Neuropsychopharmacology. 2012;37(2):478-86. PubMed PMID: 21937980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opposing roles for cannabinoid receptor type-1 (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. AU - Casarotto,Plínio C, AU - Terzian,Ana Luisa B, AU - Aguiar,Daniele C, AU - Zangrossi,Hélio, AU - Guimarães,Francisco S, AU - Wotjak,Carsten T, AU - Moreira,Fabrício A, Y1 - 2011/09/21/ PY - 2011/9/23/entrez PY - 2011/9/23/pubmed PY - 2012/4/18/medline SP - 478 EP - 86 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 37 IS - 2 N2 - The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety- and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB₁) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB₁ and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB₁-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB₁-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB₁ and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB₁ receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/21937980/Opposing_roles_for_cannabinoid_receptor_type_1__CB₁__and_transient_receptor_potential_vanilloid_type_1_channel__TRPV1__on_the_modulation_of_panic_like_responses_in_rats_ L2 - https://doi.org/10.1038/npp.2011.207 DB - PRIME DP - Unbound Medicine ER -