PMID- 27886206
OWN - NLM
STAT- MEDLINE
DCOM- 20180523
LR  - 20231111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Nov 25
TI  - The antidepressant-like activity of AC-5216, a ligand for 18KDa translocator 
      protein (TSPO), in an animal model of diabetes mellitus.
PG  - 37345
LID - 10.1038/srep37345 [doi]
LID - 37345
AB  - 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.
FAU - Qiu, Zhi-Kun
AU  - Qiu ZK
AD  - Pharmaceutical Department of the First Affiliated Hospital of Guangdong 
      Pharmaceutical University, Clinical Pharmacy Department of Guangdong 
      Pharmaceutical University, Guangzhou, 510080, P.R. China.
AD  - College of Pharmacy, Jinan University, Guangzhou 510632, P.R. China.
FAU - He, Jia-Li
AU  - He JL
AD  - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, 
      Guangzhou 510120, P.R. China.
FAU - Liu, Xu
AU  - Liu X
AD  - Pharmacy Department of General Hospital of Chinese People's Armed Police Forces, 
      Beijing 100039, P.R. China.
AD  - Academy of Military Medical Sciences, Beijing 100850, P.R. China.
FAU - Zhang, Guan-Hua
AU  - Zhang GH
AD  - Neurosurgery Department of the Third Affiliated Hospital of Southern Medical 
      University, Guangzhou 510060, P.R. China.
FAU - Zeng, Jia
AU  - Zeng J
AD  - Pharmaceutical Department of the First Affiliated Hospital of Guangdong 
      Pharmaceutical University, Clinical Pharmacy Department of Guangdong 
      Pharmaceutical University, Guangzhou, 510080, P.R. China.
FAU - Nie, Hong
AU  - Nie H
AD  - Academy of Military Medical Sciences, Beijing 100850, P.R. China.
FAU - Shen, Yong-Gang
AU  - Shen YG
AD  - Pharmaceutical Department of the First Affiliated Hospital of Guangdong 
      Pharmaceutical University, Clinical Pharmacy Department of Guangdong 
      Pharmaceutical University, Guangzhou, 510080, P.R. China.
FAU - Chen, Ji-Sheng
AU  - Chen JS
AD  - Pharmaceutical Department of the First Affiliated Hospital of Guangdong 
      Pharmaceutical University, Clinical Pharmacy Department of Guangdong 
      Pharmaceutical University, Guangzhou, 510080, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161125
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antidepressive Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (Isoquinolines)
RN  - 0 (Ligands)
RN  - 0 
      (N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide)
RN  - 0 (Purines)
RN  - 0 (Receptors, GABA-A)
RN  - 141440-82-6 (Tspo protein, rat)
RN  - BXO86P3XXW (Pregnanolone)
RN  - YNF83VN1RL (PK 11195)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Behavior, Animal/drug effects
MH  - Carrier Proteins/antagonists & inhibitors/chemistry/*metabolism
MH  - Depression/*drug therapy/etiology/metabolism
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Diabetes Mellitus, Type 2/*complications
MH  - Disease Models, Animal
MH  - Hippocampus/drug effects/metabolism
MH  - Isoquinolines/pharmacology
MH  - Ligands
MH  - Male
MH  - Molecular Weight
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Pregnanolone/metabolism
MH  - Purines/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/chemistry/*metabolism
PMC - PMC5122851
EDAT- 2016/11/26 06:00
MHDA- 2018/05/24 06:00
PMCR- 2016/11/25
CRDT- 2016/11/26 06:00
PHST- 2016/05/31 00:00 [received]
PHST- 2016/10/27 00:00 [accepted]
PHST- 2016/11/26 06:00 [entrez]
PHST- 2016/11/26 06:00 [pubmed]
PHST- 2018/05/24 06:00 [medline]
PHST- 2016/11/25 00:00 [pmc-release]
AID - srep37345 [pii]
AID - 10.1038/srep37345 [doi]
PST - epublish
SO  - Sci Rep. 2016 Nov 25;6:37345. doi: 10.1038/srep37345.