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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.)

Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the kappa-opioid receptor antagonist Nor-BNI

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Maraschina, Jhonatan Christian ; Almeida, Camila Biesdorf ; Rangel, Marcel Pereira ; Roncon, Camila Marroni ; Sestile, Caio Cesar ; Zangrossi, Jr., Helio ; Graeff, Frederico Guilherme ; Audi, Elisabeth Aparecida
Total Authors: 8
Document type: Journal article
Source: Behavioural Brain Research; v. 327, p. 75-82, JUN 1 2017.
Web of Science Citations: 3

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of K-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0 mg/kg) or intraperitoneally (2.0 mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8 nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5HT(1A)-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder. (C) 2017 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 12/23238-0 - Evaluation of cooperative mechanisms between opioidergic and serotonergic systems in the dorsal periaqueductal grey matter in the antidepressants effects
Grantee:Camila Marroni Roncon
Support Opportunities: Scholarships in Brazil - Post-Doctoral