title: Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze.
abstract: The β-adrenergic blocker and 5-HT(1A) receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT(1A) receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0mg/kg, i.p.) and paroxetine (1.5mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT(1A) antagonist, WAY-100635 (0.4 μg) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT(1A) receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder.
authors.affiliation: Department of Pharmacology and Therapeutic, State University of Maringá, Av. Colombo, 5790 - Jardim Universitário, CEP: 87020900 Maringá, PR, Brazil.
authors.forename: Vânia Ramos
authors.initials: VR
authors.lastname: Sela
authors.forename: Carla
authors.initials: C
authors.lastname: Biesdorf
authors.forename: Diego Henrique
authors.initials: DH
authors.lastname: Ramos
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.forename: Frederico Guilherme
authors.initials: FG
authors.lastname: Graeff
authors.forename: Elisabeth Aparecida
authors.initials: EA
authors.lastname: Audi
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010200:Panic / Q000187:drug effects*; D017374:Paroxetine / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000378:metabolism*; D010869:Pindolol / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D017374:Paroxetine; D010869:Pindolol; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide