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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: Neuropharmacology; v. 99, p. 620-626, DEC 2015.
• Web of Science Citations: 15

Abstract

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)

• 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
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants