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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Anti-aversive role of the endocannabinoid system in the periaqueductal gray stimulation model of panic attacks in rats

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Author(s):
Viana, Thercia G. [1] ; Hott, Sara C. [2] ; Resstel, Leonardo B. [2] ; Aguiar, Daniele C. [1] ; Moreira, Fabricio A. [1]
Total Authors: 5
Affiliation:
[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Pharmacol, BR-31270901 Belo Horizonte, MG - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pharmacol, BR-14049 Ribeirao Preto - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Psychopharmacology; v. 232, n. 9, p. 1545-1553, MAY 2015.
Web of Science Citations: 13
Abstract

Direct activation of the cannabinoid CB1 receptor in the dorsolateral periaqueductal gray (dlPAG) inhibits anxiety- and panic-related behaviours in experimental animals. It has remained unclear, however, whether the local endocannabinoid signalling is recruited as a protective mechanism against aversive stimuli. The present study tested the hypothesis that the endocannabinoid system counteracts aversive responses in the dlPAG-stimulation model of panic attacks. All drugs were infused into the dlPAG of rats. Local chemical stimulation with N-methyl-d-aspartate (NMDA, 1 nmol) was employed to induce panic-like behavioural and cardiovascular responses in freely moving and anaesthetized animals, respectively. The neuronal activity in the dlPAG was investigated by c-Fos immunohistochemistry. The selective CB1 receptor agonist, ACEA (0.005-0.5 pmol), prevented the NMDA-induced panic-like escape responses. More interestingly, increasing the local levels of endogenous anandamide with a fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3-3 nmol), prevented both the behavioural response and the increase in blood pressure induced by NMDA. The effect of URB597 (3 nmol) was reversed by the CB1 receptor antagonist, AM251 (0.1 nmol). Moreover, an otherwise ineffective and sub-threshold dose of NMDA (0.5 nmol) was able to induce a panic-like response if local CB1 receptors were previously blocked by AM251 (0.1 nmol). Finally, URB597 prevented the NMDA-induced neuronal activation of the dlPAG. The endocannabinoid system in the dlPAG attenuates the behavioural, cellular and cardiovascular consequences of aversive stimuli. This process may be considered for the development of additional treatments against panic and other anxiety-related disorders. (AU)

FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
Grantee:Francisco Silveira Guimaraes
Support Opportunities: Research Projects - Thematic Grants