title: Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors.
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 μ-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.
authors: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil.
authors: Camila Marroni
authors: CM
authors: Roncon
authors: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil.
authors: Rafael Carvalho
authors: RC
authors: Almada
authors: Laboratory of Psychopharmacology, Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil.
authors: Jhonatan Christian
authors: JC
authors: Maraschin
authors: Laboratory of Psychopharmacology, Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná 87020-900, Brazil.
authors: Elisabeth Aparecida
authors: EA
authors: Audi
authors: Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors: Hélio
authors: H
authors: Zangrossi
authors: Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil; Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors: Frederico Guilherme
authors: FG
authors: Graeff
authors: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, São Paulo 14050-220, Brazil; Neurobiology of Emotions Research Centre (NAP-USP-NuPNE), Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil. Electronic address: nccoimbr@fmrp.usp.br.
authors: Norberto Cysne
authors: NC
authors: Coimbra
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009292:Narcotic Antagonists / Q000494:pharmacology; D009483:Neuropsychological Tests; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011619:Psychotropic Drugs; D017450:Receptors, Opioid, mu; D005473:Fluoxetine; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin
keywords: 5-HT(1A) receptor; Dorsal periaqueductal gray matter; Elevated T-maze; Fluoxetine; Panic; μ-opioid receptor