We have established an animal model for
olanzapine-induced
body weight gain, and used it to explore the relation between this
weight gain, excessive food consumption, gross motor activity, and macronutrient choice. Female Sprague-Dawley rats received
olanzapine (
OLAN) or diluent (1.2mg/kg per day) via gavage for 10 days. Rats receiving
OLAN exhibited significant increases in
body weight when compared with control rats.
Body weight returned to control levels once
OLAN treatment was discontinued. Food consumption among the
OLAN-treated group was significantly greater than among control rats between 6 and 10 days of treatment. Between 4 and 10 days of treatment, feed efficiency (grams of weight gained/grams of food consumed) was also significantly greater among animals receiving
OLAN. In contrast, chronic administration of
haloperidol (0.04mg/kg; q.d.; gavage) did not influence
body weight or food consumption of treated rats. Gross motor activity was significantly reduced by
OLAN between 1 and 10 days of treatment, also returning to control levels when treatment was discontinued. No significant changes were observed in brain DA,
DOPAC, HVA or
5-HIAA among animals receiving
OLAN daily for 30 days; however,
5-HT levels were significantly elevated. In contrast, acute (1.2mg/kg; 2h; i.p.) administration of
OLAN significantly increased brain
DOPAC and HVA levels without affecting those of
5-HT or
5-HIAA.
OLAN (1.2mg/kg; q.d.; 10 days) administration did not alter macronutrient choice (
carbohydrate:
protein ratio) of rats. These data show that an animal model of
OLAN-induced
weight gain is readily generated, and suggest that the
weight gain results at least in part from increased food intake, reduced gross motor activity, and enhanced feed efficiency.