Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats

Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine but also histamine muscarin and a adrenergic receptors In humans Olanzapine induces weight gain and increases the risk of type 2 diabetes The underlying mechanisms of Olanzapine-induced weight gain are unclear To study this we administered Olanzapine (5 mg/kg) in female Wistar rats on a medium fat diet for 14 days via a permanent gastric catheter twice a day Just prior to the onset and at the middle of dark phase Food end water intake locomotor activity and body temperature were measured Olanzapine acutely induced hypothermia markedly decreased locomotor activity and increased body weight during 14 days of treatment Olanzapine treatment did not result in an alteration of 24 h food Intake but diurnal patterns of feeding behavior and body temperature were dramatically changed We conclude that in female Wistar rats Olanzapine has an acute hypothermic effect that the effect of Olanzapine on feeding behavior is secondary to the effect on activity and that Olanzapine-induced weight gain is primarily the result of reduction in locomotor activity (C) 2010 Elsevier Inc All rights reserved