Abstract
Diabetes mellitus is a chronic disease that is associated with depression. Also, depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator protein (18kDa) (TSPO) and allopregnanolone play an important role in the depression treatment. However, few studies have evaluated TSPO and allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The present study aimed to explore antidepressant-like effects of AC-5216 on diabetic rats. Following the development of diabetic model induced by high fat diet (HFD) feeding and streptozotocin (STZ), AC-5216 (0.3 and 1 mg/kg, i.g.) elicited the antidepressant-like effects in behavioral tests while these activities were blocked by TSPO antagonist PK11195 (3 mg/kg, i.p.). The levels of allopregnanolone in the prefrontal cortex and hippocampus were increased by AC-5216 (0.3 and 1 mg/kg, i.g.), which was antagonized by PK11195 (3 mg/kg, i.p.). The increased plasma glucose (PG) and decreased insulin (INS) in HFD-STZ rats were reversed by AC-5216 (0.3 and 1 mg/kg, i.g.). This study indicates that the antidepressant-like effects of AC-5216 on HFD-STZ rats, suggesting that TSPO may represent a novel therapeutic target for depression in T2DM.
Highlights
Despite a variety of psychological and pharmacological treatments have been introduced in depression with type 2 diabetes mellitus (T2DM), a large proportion of patients had not achieved satisfactory outcomes
The antidepressant-like effects were assessed by animal behavioral tests, including sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), forced swimming test (FST) and open-field test (OFT)
The results indicated that the antidepressant-like effects of AC-5216 in high fat diet (HFD)-STZ rats were associated with allopregnanolone biosynthesis in the prefrontal cortex and hippocampus, which was mediated by Translocator protein 18kDa (TSPO)
Summary
Despite a variety of psychological and pharmacological treatments have been introduced in depression with T2DM, a large proportion of patients had not achieved satisfactory outcomes. Translocator protein 18kDa (TSPO), previously described as peripheral-type benzodiazepine receptor (PBR), represents the starting point and an important rate-limiting step in neurosteroidogenesis[19]. It is a five trans-membrane domain protein that is located mainly in the outer mitochondrial membrane in peripheral tissues and central nervous system (CNS). TSPO activation was effective in ameliorating the severity of diabetic neuropathy by means of increased levels of neuroactive steroid[23]. To further evaluate the role of TSPO in the treatment of depression in T2DM, we determined whether pharmacological effects of AC-5216 were antagonized by PK11195 (TSPO antagonist) in HFD-STZ rats. The levels of allopregnanolone, plasma glucose (PG), insulin (INS), total cholesterol (TC), and triglyceride (TG) were assessed as well
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call