title: The antidepressant-like activity of AC-5216, a ligand for 18KDa translocator protein (TSPO), in an animal model of diabetes mellitus.
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.
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou, 510080, P.R. China.|College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Qiu
authors.affiliation: Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, P.R. China.
authors.forename: Jia-Li
authors.initials: JL
authors.lastname: He
authors.affiliation: Pharmacy Department of General Hospital of Chinese People's Armed Police Forces, Beijing 100039, P.R. China.|Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Neurosurgery Department of the Third Affiliated Hospital of Southern Medical University, Guangzhou 510060, P.R. China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou, 510080, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Academy of Military Medical Sciences, Beijing 100850, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Nie
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou, 510080, P.R. China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Shen
authors.affiliation: Pharmaceutical Department of the First Affiliated Hospital of Guangdong Pharmaceutical University, Clinical Pharmacy Department of Guangdong Pharmaceutical University, Guangzhou, 510080, P.R. China.
authors.forename: Ji-Sheng
authors.initials: JS
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D008970:Molecular Weight; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011280:Pregnanolone / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D002352:Carrier Proteins; D007546:Isoquinolines; D008024:Ligands; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D011687:Purines; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D011280:Pregnanolone; C037850:PK 11195