Efficacy of olanzapine and haloperidol in an animal model of mania.
OBJECTIVE
Intracerebroventricular (ICV) administration of ouabain, a potent sodium pump inhibitor, has been used to model mania. Antipsychotic agents have demonstrated efficacy in the management of acute mania. This study was undertaken to determine the prophylactic efficacy of olanzapine and haloperidol in the ouabain mania model.


METHODS
Male Sprague-Dawley rats (4-8/group) were treated with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open field locomotion was quantified at baseline and after ouabain administration.


RESULTS
Ouabain caused a significant increase in open field locomotion (253.7+/-SEM 55.12 vs control 53.1+/-12.13 squares traversed in 30 min in the olanzapine experiments, P<0.05; and 236.5+/-41.42 vs 129.3+/-38.23, P<0.05 in the haloperidol experiments). Olanzapine alone at low dose (102.2+/-37.7) or high dose (151.2+/-49.2) did not alter open field activity. Low dose olanzapine (176.6+/-73.27) but not high dose (307.5+/-167.32) caused a modest reduction of the ouabain effect. Haloperidol alone significantly reduced motoric activity compared to control (55.6+/-18.0, P<0.05), and prevented ouabain-induced hyperactivity (60.3+/-33.1, P<0.05).


CONCLUSIONS
Haloperidol, but not olanzapine, demonstrated efficacy in this mania model, but methodological details may have reduced the effect of olanzapine.
El-Mallakh
Rif S
RS
Mood Disorders Research Program, University of Louisville School of Medicine, Louisville, Kentucky 40292, United States. rselma01@athena.louisville.edu <rselma01@athena.louisville.edu>
Decker
Sarah
S
Morris
Matthew
M
Li
Xiao-Ping
XP
Huff
Mary O'Malley
MO
El-Masri
M Adnan
MA
Levy
Robert S
RS
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004341:Drug Evaluation; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000627:therapeutic use*; D008297:Male; D000077152:Olanzapine; D010042:Ouabain / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D001569:Benzodiazepines; D010042:Ouabain; D006220:Haloperidol; D000077152:Olanzapine