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

Autor(es)

Maraschina, Jhonatan Christian ; Almeida, Camila Biesdorf ; Rangel, Marcel Pereira ; Roncon, Camila Marroni ; Sestile, Caio Cesar ; Zangrossi, Jr., Helio ; Graeff, Frederico Guilherme ; Audi, Elisabeth Aparecida

• Tipo de documento: Artigo Científico
• Fonte: Behavioural Brain Research; v. 327, p. 75-82, JUN 1 2017.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 12/23238-0 - Avaliação de mecanismos cooperativos entre os sistemas opioidérgico e o serotoninérgico na substância cinzenta periaqueductal dorsal nos efeitos de antidepressivos
• Beneficiário: Camila Marroni Roncon
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado