Clin Psychopharmacol Neurosci 2019; 17(2): 314-317  
Adjunctive Lurasidone Suppresses Food Intake and Weight Gain Associated with Olanzapine Administration in Rats
Gavin P. Reynolds1, Caroline F. Dalton1, William Watrimez2, Joshua Jackson2, Michael K. Harte2
1Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, 2Division of Pharmacy and Optometry, School of Health Sciences, Manchester, UK
Correspondence to: Gavin P. Reynolds, PhD Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB., UK
Tel: +44-114-225-5555, Fax: +44-114-225-4449 E-mail: gavin.reynolds@hotmail.com
ORCID: https://orcid.org/0000-0001-9026-7726
Received: February 22, 2018; Revised: April 2, 2018; Accepted: April 3, 2018; Published online: May 31, 2019.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: Lurasidone is an antipsychotic drug that shows a relative lack of weight gain common to many antipsychotics. Aripiprazole and ziprasidone also show little weight gain and can reduce olanzapine-induced food intake and weight gain in animals, paralleling some clinical findings. We hypothesized that lurasidone would have similar actions.
Methods: Female Lister-hooded rats received intraperitoneal injection either 2× vehicle (saline), lurasidone (3 mg/kg) and vehicle, olanzapine (1 mg/kg) and vehicle, or olanzapine and lurasidone. Following drug administration food intake was measured for 60min. A further series of rats underwent a seven-day regime of once-daily administration of the above doses and free access to food and water. Weight gain over the course of the study was monitored.
Results: Olanzapine induced a significant increase in food intake while lurasidone showed no significant effect. Co-administration of lurasidone with olanzapine suppressed the increase in food intake. Repeated dosing showed an increase in body weight after seven days with olanzapine, and no significant effect observed with lurasidone, while repeated administration of lurasidone with olanzapine reduced the effect of olanzapine on the increase in body weight.
Conclusion: These findings support our hypotheses in that lurasidone, in addition to a lack of effect on acute food intake and short term weight gain, can reduce olanzapine-induced food intake and weight gain in rats. This indicates the drug to have an active anti-hyperphagic mechanism, rather than solely the absence of a drug-induced weight gain that is such a severe limitation of drugs such as olanzapine.
Keywords: Antipsychotic agents; Eating; Weight gain; Lurasidone hydrochloride; Olanzapine.


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