title: Panicolytic-like effect of tramadol is mediated by opioid receptors in the dorsal periaqueductal grey.
abstract: Tramadol is a synthetic opioid prescribed for the treatment of moderate to severe pain, acting as agonist of μ-opioid receptors and serotonin (5-HT) and noradrenaline (NE) reuptake inhibitor. This study evaluated the effects of tramadol in rats submitted to the elevated T-maze (ETM), an animal model that evaluates behavioural parameters such as anxiety and panic. Male Wistar rats were intraperitoneally (i.p.) treated acutely with tramadol (16 and 32mg/kg) and were submitted to the ETM. Tramadol (32mg/kg) promoted a panicolytic-like effect. Considering that dorsal periaqueductal grey (dPAG) is the main brain structure related to the pathophysiology of panic disorder (PD), this study also evaluated the participation of 5-HT and opioid receptors located in the dPAG in the panicolytic-like effect of tramadol. Seven days after stereotaxic surgery for implantation of a cannula in the dPAG, the animals were submitted to the test. To assess the involvement of 5-HT1Areceptors on the effect of tramadol, we combined the 5-HT1Areceptor antagonist, WAY100635 (0.37nmol), microinjected intra-dPAG, 10min prior to the administration of tramadol (32mg/kg, i.p.). WAY100635 did not block the panicolytic-like effect of tramadol. We also associated the non-selective opioid receptor antagonist, naloxone, systemically (1mg/kg, i.p.) or intra-dPAG (0.5nmol) administered 10min prior to tramadol (32mg/kg, i.p.). Naloxone blocked the panicolytic-like effect of tramadol in both routes of administrations, showing that tramadol modulates acute panic defensive behaviours through its interaction with opioid receptors located in the dPAG.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil. Electronic address: gisouzafiaes@gmail.com.
authors.forename: Gislaine Cardoso de Souza
authors.initials: GCS
authors.lastname: Fiaes
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
authors.forename: Camila Marroni
authors.initials: CM
authors.lastname: Roncon
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
authors.forename: Caio Cesar
authors.initials: CC
authors.lastname: Sestile
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
authors.forename: Jhonatan Christian
authors.initials: JC
authors.lastname: Maraschin
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil.
authors.forename: Rodolfo Luis Silva
authors.initials: RLS
authors.lastname: Souza
authors.affiliation: Department of Medicine, State University of Maringá, Maringá, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Porcu
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil. Electronic address: elisabethaudi8@gmail.com.
authors.forename: Elisabeth Aparecida
authors.initials: EA
authors.lastname: Audi
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010200:Panic / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010879:Piperazines; D011725:Pyridines; D017450:Receptors, Opioid, mu; D058829:Serotonin 5-HT1 Receptor Antagonists; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D009270:Naloxone; D014147:Tramadol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: Dorsal periaqueductal grey; Elevated T-maze; Panic disorder; Tramadol