Intracerebroventricular administration of ouabain as a model of mania in rats.
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.
El-Mallakh
Rif S
RS
Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, Louisville, KY 40292, USA. rselma01@athena.louisville.edu
El-Masri
M Adnan
MA
Huff
Mary O'Malley
MO
Li
Xiao-Ping
XP
Decker
Sarah
S
Levy
Robert S
RS
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
D004791:Enzyme Inhibitors; D010042:Ouabain; D008094:Lithium