Depression-like behaviors in mice subjected to co-treatment of high-fat diet and corticosterone are ameliorated by AICAR and exercise

Abstract

Major depressive disorder (MDD) and type II diabetes mellitus (T2DM) are highly co-morbid, and there may be a bi-directional connection between the two. Herein, we have described a mouse model of a depression-like and insulin-resistant (DIR) state induced by the co-treatment of high-fat diet (HFD) and corticosterone (CORT). 5-Aminoimidazole-4-carboxamide-1-β-d- ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), was originally used to improve insulin resistance (IR). Interestingly, our results show a clear potential for AICAR as a putative antidepressant with a chronic action on the DIR mice. In contrast to the traditional antidepressants, AICAR as a promising antidepressant avoids reducing insulin actions of skeletal muscle in the context of long-term HFD. Exercise also produced antidepressant effects. Our data suggest that the effects of AICAR and exercise on DIR may further increase our understanding on the link between depression and diabetes.

Keywords: 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside; AICAR; AMPK; CD; CNS; CORT; Corticosterone; DIR; Depression; Exercise; FST; Forced Swim Test; HFD; High-fat diet; IR; ITT; Insulin Tolerance Tests; MDD; NSF; Novelty Suppressed Feeding; OFT; Open Field Test; SSRI; T2DM; adenosine 5ʹ-monophosphate-activated protein kinase; central nervous system; control diet; corticosterone; depression-like and insulin-resistant; high-fat diet; insulin-resistant; major depressive disorder; selective serotonin reuptake inhibitors; type II diabetes mellitus.