title: Effects of diphenyl diselenide on depressive-like behavior in ovariectomized mice submitted to subchronic stress: involvement of the serotonergic system.
abstract: BACKGROUND
  The transition to menopause is associated with an increased risk of depressed mood.
  
  
  OBJECTIVE
  This study was conducted to investigate whether diphenyl diselenide [(PhSe)₂] treatment could reduce the effects of postmenopausal depression-like behavior in ovariectomized female mice submitted to subchronic stress exposure.
  
  
  METHODS
  Mice were divided into four groups: sham, (PhSe)₂, ovariectomy (OVX), and OVX + (PhSe)₂. Animals were ovariectomized/sham-operated and subjected to stress session once a day for 7 days from the fifth to the 11th day after OVX. The behavioral tests (open field, tail suspension (TST), and forced swimming (FST)) were performed on the 14th day after OVX. Mice were treated orally once a day with vehicle (canola oil, 10 ml/kg) or (PhSe)₂ (10 mg/kg; 10 ml/kg) 30 min before being exposed to subchronic stress, or from the 11th to the 14th day. Paroxetine (8 mg/kg i.p.) and pargyline (30 mg/kg i.p.) were used as positive controls. The involvement of serotonergic receptor subtypes in the antidepressant-like effect of (PhSe)₂ was assessed in the FST using WAY 100635 (0.1 mg/kg s.c.), ritanserin (1 mg/kg i.p.), and ondansetron (1 mg/kg i.p.) as serotonergic antagonists. Monoamine oxidase (MAO) A and B activities were also determined.
  
  
  RESULTS
  The prolongation of immobility time in TST and FST in OVX mice submitted to subchronic stress was prevented by (PhSe)₂ treatment. Ritanserin and ondansetron blocked the antidepressive-like effect of (PhSe)₂, suggesting the involvement of 5-HT(2A/2C) and 5-HT₃ receptor subtypes. Both paroxetine and pargyline were effective in reducing the immobility time of stressed OVX mice in the FST. No alterations in locomotor activity were observed. Although (PhSe)₂ had inhibited in vitro MAO-A and MAO-B activities, none of the groups presented alterations neither in ex vivo MAO-A nor in MAO-B activity.
  
  
  CONCLUSIONS
  (PhSe)₂ treatment could influence mood and behavior, indicating a promising role of this organoselenium compound in the management of postmenopausal depressive symptoms.
authors.affiliation: Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 Rio Grande do Sul, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Trevisan da Rocha
authors.forename: Bibiana
authors.initials: B
authors.lastname: Mozzaquatro Gai
authors.forename: Simone
authors.initials: S
authors.lastname: Pinton
authors.forename: Tuane
authors.initials: T
authors.lastname: Bazanella Sampaio
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001555:Benzene Derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003863:Depression / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D046353:Immobility Response, Tonic / Q000187:drug effects; D008593:Menopause / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017294:Ondansetron / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010052:Ovariectomy / Q000523:psychology*; D010293:Pargyline / Q000494:pharmacology / Q000627:therapeutic use; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D016713:Ritanserin; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000201:enzymology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D000928:Antidepressive Agents; D001555:Benzene Derivatives; D008996:Monoamine Oxidase Inhibitors; D016566:Organoselenium Compounds; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D016713:Ritanserin; C061132:diphenyldiselenide; D017374:Paroxetine; D017294:Ondansetron; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D010293:Pargyline; D008995:Monoamine Oxidase