Evaluating the Effect of Orlistat Administration on Depressive Behavior in Mice Following Inducing Depression by Water Avoidance Stress Model

The weight-loss drugs can induce depression. Orlistat is one of the common weight-loss drugs, but preclinical studies about its effect on mood have not been performed. The aim of this study was evaluating the effect of orlistat alone and following inducing stress on mice depressive behavior.

In this fundamental-applied study, male white mice (27±2 g), in six groups having 7 animals were used. Orlistat was administered orally and imipramine (positive control) was injected intraperitonealy daily, depression was induced by the water avoidance stress (WAS) model during 14 days. The activity was evaluated by the Locomotor Activity Test, depression was assessed by measuring the immobility time during the forced swimming test (FST), food consumption in novelty suppressed feeding test (NSFT), and the sucrose preference test.

Orlistat (25 mg/kg) did not change the locomotor activity. Stress increased the duration of immobility in the forced swimming test compared to the stress control group (98±2.2 seconds, P<0.001). The difference in immobility time between orlistat group and the control group was insignificant, the difference in immobility time between orlistat-WAS group and WAS alone group was also insignificant (P>0.05). The difference in the results of latency and food consumption during novelty suppressed feeding test in orlistat group compared to the control group and between orlistat-WAS group compared with the WAS alone group were insignificant. In orlistat-WAS group the sucrose preference increased (69/8 %). Imipramine reduced depressive behavior in mice.

Orlistat administration did not induce depressive behavior in animals and it did not augment depression when administered during WAS. Evaluating the effect of chronic orlistat administration on depressive behavior is suggested.