title: An animal model of antipsychotic-induced weight gain.
abstract: 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.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, MIT E25-604, 45 Carleton Street, Cambridge, MA 02139, USA.
authors.forename: Anibal A
authors.initials: AA
authors.lastname: Arjona
authors.forename: Sandy X
authors.initials: SX
authors.lastname: Zhang
authors.forename: Brittany
authors.initials: B
authors.lastname: Adamson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wurtman
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001522:Behavior, Animal; D001569:Benzodiazepines / Q000009:adverse effects*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003624:Darkness; D004298:Dopamine / Q000032:analysis; D004435:Eating / Q000187:drug effects; D004563:Electrochemistry / Q000379:methods; D005260:Female; D005518:Food Preferences / Q000187:drug effects; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D017440:Photoperiod; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D001569:Benzodiazepines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000077152:Olanzapine; D004298:Dopamine; D006719:Homovanillic Acid