Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter mu-opioid receptors

Autor(es)

Roncon, Camila Marroni ^{[1, 2]} ; Almada, Rafael Carvalho ^{[1, 2]} ; Maraschin, Jhonatan Christian ^[3] ; Audi, Elisabeth Aparecida ^[3] ; Zangrossi, Jr., Helio ^{[4, 5]} ; Graeff, Frederico Guilherme ^{[1, 5]} ; Coimbra, Norberto Cysne ^{[1, 2, 5]}

Afiliação do(s) autor(es)

^[1] Behav Neurosci Inst INeC, BR-14050220 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Estadual Maringa, Dept Pharmacol & Therapeut, Lab Psychopharrnacol, BR-87020900 Maringa, Parana - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo FMRP USP, Ribeirao Preto Sch Med, Neurobiol Emot Res Ctr NAP USP NuPNE, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropharmacology; v. 99, p. 620-626, DEC 2015.
• Citações Web of Science: 15

Resumo

Previously reported results have shown that the inhibitory effect of fluoxetine on escape behavior, interpreted as a panicolytic-like effect, is blocked by pretreatment with either the opioid receptor antagonist naloxone or the 5-HT1A receptor (5-HT1A-R) antagonist WAY100635 via injection into the dorsal periaqueductal gray matter (dPAG). Additionally, reported evidence indicates that the mu-opioid receptor (MOR) interacts with the 5-HT1A-R in the dPAG. In the present work, pretreatment of the dPAG with the selective MOR blocker CTOP antagonized the anti-escape effect of chronic fluoxetine (10 mg/kg, i.p., daily, for 21 days), as measured in the elevated T-maze (ETM) test, indicating mediation of this effect by the MOR. In addition, the combined administration of sub-effective doses of the selective MOR agonist DAMGO (intra-dPAG) and sub-effective doses of chronic as well as subchronic (7 days) fluoxetine increased avoidance and escape latencies, suggesting that the activation of MORs may facilitate and accelerate the effects of fluoxetine. The current observation that MORs located in the dPAG mediate the anti-escape effect of fluoxetine may open new perspectives for the development of more efficient and fast-acting panic-alleviating drugs. (C) 2015 Elsevier Ltd. 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
• Processo FAPESP: 12/03798-0 - Envolvimento de receptores opióides e endocanabinóides da substância negra na modulação da atividade da via GABAérgica nigro-tectal durante a organização do comportamento de defesa eliciado por roedores confrontados com serpentes veneníferas
• Beneficiário: Norberto Cysne Coimbra
• Modalidade de apoio: Auxílio à Pesquisa - Regular