title: Serotonergic systems are implicated in antinociceptive effect of m-trifluoromethyl diphenyl diselenide in the mouse glutamate test.
abstract: The organoselenium compound m-trifluoromethyl diphenyl diselenide (m-CF3-PhSe)2 has antinociceptive actions in several animal models, which are mediated by interaction with endogenous opioid systems. It also shows antidepressant-like action mediated by both opioid and serotonergic systems. Considering that serotonin (5-HT) plays an important role in the descending control of pain, this study further investigated the role of serotonergic systems in the antinociceptive action of (m-CF3-PhSe)2 in the glutamate-induced licking behavior model in mice. (m-CF3-PhSe)2 (1-50 mg/kg, p.o.), morphine (2.5 mg/kg, s.c.) or paroxetine (5 mg/kg, i.p.) reduced glutamate-induced nociception. Selective 5-HT1A and 5-HT2A receptor antagonists, WAY100635 (0.7 mg/kg, i.p.) and ketanserin (0.3 mg/kg, i.p.), but not the selective 5-HT3 receptor antagonist, ondansetron (0.5 mg/kg, i.p.), prevented the antinociceptive effect of (m-CF3-PhSe)2 (10 mg/kg) in the glutamate test. In biochemical studies, (m-CF3-PhSe)2 (10 and 50 mg/kg) decreased [(3)H]5-HT uptake in crude synaptosomes of mouse brains and slightly inhibited in vitro [(3)H]5-HT binding. In kinetic studies, the selenium (Se) distribution was determined at different time points after the administration of (m-CF3-PhSe)2 (500 mg/kg, p.o.) to mice. After 30 min, a high amount of Se was found in liver and kidneys, followed by the lung, red blood cells, serum and brain. A significant amount of Se accumulated in fat over the course of 8h. Urine was an important route of Se excretion originating from (m-CF3-PhSe)2. Collectively, results of this study indicate an involvement of the serotonergic systems in the antinociceptive effect of (m-CF3-PhSe)2 and a wide distribution of Se derived from this compound.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil.
authors.forename: César Augusto
authors.initials: CA
authors.lastname: Brüning
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil.
authors.forename: Bibiana Mozzaquatro
authors.initials: BM
authors.lastname: Gai
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil.
authors.forename: Suelen Mendonça
authors.initials: SM
authors.lastname: Soares
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Martini
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil. Electronic address: criswn@quimica.ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D018698:Glutamic Acid; D051379:Mice; D017646:Organosilicon Compounds / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D012643:Selenium / Q000032:analysis; D059326:Serotonergic Neurons / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000700:Analgesics; D017646:Organosilicon Compounds; C546861:m-trifluoromethyl-diphenyl diselenide; D012701:Serotonin; D018698:Glutamic Acid; D012643:Selenium
keywords: Antinociceptive; Distribution; Glutamate test; Organoselenium; Selenium; Serotonergic systems