A model for antipsychotic-induced obesity in the male rat.
BACKGROUND
Weight gain is a common and severe side effect of antipsychotic drugs. A usual tool to study the side effects of psychotropic drugs is animal models. However, attempts to create an animal model of antipsychotic-induced weight gain were not successful so far. Female rodents are sensitive to the effects of antipsychotics, but not males. This does not match the human clinical situation. Antipsychotics have different pharmacokinetic properties in rats and humans, and rats and humans have different spontaneous diets.


METHODS
In the present study, we tested the hypothesis that the insensitivity of male rats to the weight-promoting effects of antipsychotics could be related to the mode of administration of antipsychotics and to the animals' diet. Antipsychotics were mixed with the food, and rats were fed a diet resembling the human diet. Rats were treated with 0.01, 0.1, 0.5, and 2 mg/kg of olanzapine or with a control solution for 6 weeks. Their weight and food intake were recorded, and their body composition were analyzed. The effects on weight and food intake of olanzapine (1 mg/kg), haloperidol (1 mg/kg), and ziprasidone (10 mg/kg) were also compared in a 3-week treatment experiment.


RESULTS
The results showed that 0.5 and 2 mg of olanzapine, but not lower doses, increase body weight and subcutaneous fat deposition. After the 3-week treatment, olanzapine-treated rats, but not haloperidol- or ziprasidone-treated rats, had significantly increased their weight.


CONCLUSIONS
This study shows that a rat model of obesity induced by antipsychotics can be created under specific conditions of drug administration, diet, and dose.
Minet-Ringuet
Julie
J
Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, 54 Avenue de la République, Villejuif, France.
Even
Patrick C
PC
Lacroix
Magali
M
Tomé
Daniel
D
de Beaurepaire
Renaud
R
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006220:Haloperidol / Q000009:adverse effects; D008297:Male; D009765:Obesity / Q000139:chemically induced* / Q000503:physiopathology; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000009:adverse effects; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; C092292:ziprasidone; D006220:Haloperidol; D000077152:Olanzapine