Creatine and α-lipoic acid improved dexamethasone-induced depressive-like behavioral parameters in mice

Abstract

Corticosterone treatment in mice impairs mitochondrial function, decreases energy production in the brain, and induces depressive-like behaviors. Creatine (Crt) is vital for energy homeostasis in the brain. Alpha-lipoic acid (ALA) improves mitochondrial function and reduces oxidative stress. The aim was investigating the effect of Crt and ALA following dexamethasone (Dexa) induced depression in mice model of despair. Female mice (22±3 g) were experimented. Dexa (15 mcg/kg, SC) injected for a week, Crt was inserted in animals’ diet, and ALA (25, 50 mg/kg) injected IP. After the locomotor test, behavioral parameters of depression, including immobility time during the forced swimming test (FST), and anhedonia during the sucrose preference test were evaluated. No significant changes were recorded during the locomotor test. Dexa increased the immobility time during the FST (154 ± 6.3 s vs control 119±5.5 s, p<0.05). Crt 2 , reduced immobility time (89 ± 7 s vs normal diet 125 ± 4.7 s, p<0.01), ALA (50 mg/kg) reduced the immobility time (88 ± 15 vs control 134±8 s, p<0.05). While, Crt and ALA co-administration with Dexa reduced the immobility time during the FST. The results of the sucrose preference test were in line with FST, since Crt and ALA increased the sucrose preference when administered together with Dexa. Improvement of behavioral parameters in mice treated with Crt and ALA clearly indicates their effect on preventing Dexa depressive-like behaviors. Mitochon-drial dysfunction must be further evaluated regarding Dexa induced depressive behavior. © 2021, Hacettepe University, Faculty of Pharmacy. All rights reserved.