title: Intracerebroventricular administration of ouabain as a model of mania in rats.
abstract: BACKGROUND
  Human bipolar illness is characterized by mood state- and diagnosis-associated abnormalities of cellular cation distribution and transport. These include reduced sodium pump activity and expression and increased intracellular sodium. If these alterations are related to the pathophysiology of the disease, rather than secondary or ancillary abnormalities, then one would expect that modeling of these changes in vivo would produce lithium-preventable behavioral abnormalities.
  
  
  METHODS
  Ouabain, a potent inhibitor of the sodium pump, was administered intracerebroventricularly to male rats previously fed lithium-containing food or plain rat chow. Locomotion was then quantified in an open field.
  
  
  RESULTS
  Ouabain increased locomotion 300% over baseline. Lithium pretreatment prevented the ouabain-induced hyperlocomotion response.
  
  
  CONCLUSIONS
  Inhibition of central nervous system sodium pump with ouabain produces a plausible animal model of mania. This model may be useful for preclinical screening of potential mood stabilizers.
authors.affiliation: Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40292, USA. rselma01@athena.louisville.edu
authors.forename: Rif S
authors.initials: RS
authors.lastname: El-Mallakh
authors.forename: M Adnan
authors.initials: MA
authors.lastname: El-Masri
authors.forename: Mary O'Malley
authors.initials: MO
authors.lastname: Huff
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Li
authors.forename: Sarah
authors.initials: S
authors.lastname: Decker
authors.forename: Robert S
authors.initials: RS
authors.lastname: Levy
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007276:Injections, Intraventricular; D008094:Lithium / Q000097:blood / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010042:Ouabain / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D010042:Ouabain; D008094:Lithium