Early perturbation in feeding behaviour and energy homeostasy in olanzapine-treated rats.
BACKGROUND
The antipsychotic drug, olanzapine, often induces weight gain and glucose metabolism disturbances, which may result from feeding pattern abnormalities.


OBJECTIVE
The objectives of the study were to examine the effects of a chronic olanzapine treatment on feeding patterns in the rat and to investigate a potential time-related association between feeding patterns and the appearance of glucose metabolism abnormalities and adiposity.


METHODS
Male rats were treated with olanzapine (2 mg/kg/day), haloperidol (1 mg/kg/day) or a control solution (drugs mixed with the food). In experiment 1, treatments lasted 26 days and feeding patterns were measured on day 21. In experiment 2, treatments lasted for 46 days, and an oral glucose tolerance test (OGTT) was realised on day 31. At the end of both experiments, plasma parameters and body composition were analysed.


RESULTS
In experiment 1, olanzapine-treated animals showed increased meal number, decreased ingestion rate, meal size and inter-meal interval, and no change in total food intake. Plasma glucose, OGTT and body composition were not altered. In experiment 2, after 31 days of treatment, fasting blood glucose was increased and OGTT indicated an insulin resistance. After 46 days of treatment, hyperglycaemia was aggravated (compared to 31 days), and adiposity was increased in olanzapine-treated animals. In both experiments, the haloperidol-treated rats did not differ from the control ones.


CONCLUSIONS
Chronic olanzapine treatment produces changes in feeding patterns, in a way consistent with an increased incentive drive to eat. As a whole, the results raise the hypothesis that long-term alteration of feeding pattern by olanzapine may predispose to disturbances in the regulation of energy metabolism.
Victoriano
Montserrat
M
UMR914 Physiologie de la Nutrition et du Comportement Alimentaire, INRA, 16 rue Claude Bernard, 75005, Paris, France.
Hermier
Dominique
D
Even
Patrick C
PC
Fromentin
Gilles
G
Huneau
Jean-François
JF
Tomé
Daniel
D
de Beaurepaire
Renaud
R
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D005951:Glucose Tolerance Test; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012565:Schizophrenic Psychology; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D001786:Blood Glucose; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine