title: Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus.
abstract: BACKGROUND
  Alterations in brainstem circuits have been proposed as a possible mechanism underlying the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder.
  
  
  OBJECTIVE
  The aim of this study is to assess the effect of chronic lithium treatment on behavioral disinhibition induced by MnR lesions.
  
  
  METHODS
  MnR electrolytic lesions were performed in C57BL/6J mice, with sham-operated and intact animals as control groups. Following recovery, mice were chronically treated with lithium (LiCl, added in chow) followed by behavioral testing.
  
  
  RESULTS
  MnR lesion induced manic-like behavioral alterations including hyperactivity in the open field (OF), stereotyped circling, anxiolytic/risk taking in the elevated plus maze (EPM) and light/dark box (LDB) tests, and increased basal body temperature. Lithium was specifically effective in reducing OF hyperactivity and stereotypy but did not reverse (EPM) or had a nonspecific effect (LDB) on anxiety/risk-taking measures. Additionally, lithium decreased saccharin preference and prevented weight loss during single housing.
  
  
  CONCLUSIONS
  Our data support electrolytic lesions of the MnR as an experimental model of a hyper-excitable/disinhibited phenotype consistent with some aspects of mania that are attenuated by the mood stabilizer lithium. Given lithium's relatively specific efficacy in treating mania, these data support the hypothesis that manic symptoms derive not only from the stimulation of excitatory systems but also from inactivation or decreased activity of inhibitory mechanisms.
authors.affiliation: Instituto de Psicologia, Universidade de São Paulo, Av. Prof. Mello Moraes 1721, Sala A-6, Cidade Universitária, 05508-900, São Paulo, SP, Brazil.
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Pezzato
authors.forename: Adem
authors.initials: A
authors.lastname: Can
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Hoshino
authors.forename: José de Anchieta C
authors.initials: Jde A
authors.lastname: Horta
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Mijares
authors.forename: Todd D
authors.initials: TD
authors.lastname: Gould
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000473:pathology / Q000523:psychology; D004564:Electrocoagulation / Q000009:adverse effects* / Q000379:methods; D006948:Hyperkinesis / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000473:pathology*; D013239:Stereotyped Behavior / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D014151:Anti-Anxiety Agents; D018021:Lithium Chloride