PMID- 29464572
OWN - NLM
STAT- MEDLINE
DCOM- 20190313
LR  - 20240204
IS  - 1878-7479 (Electronic)
IS  - 1933-7213 (Print)
IS  - 1878-7479 (Linking)
VI  - 15
IP  - 2
DP  - 2018 Apr
TI  - Brain Renin-Angiotensin System Blockade Attenuates Methamphetamine-Induced 
      Hyperlocomotion and Neurotoxicity.
PG  - 500-510
LID - 10.1007/s13311-018-0613-8 [doi]
AB  - Methamphetamine (METH) abuse has become a major public health concern worldwide 
      without approved pharmacotherapies. The brain renin-angiotensin system (RAS) is 
      involved in the regulation of neuronal function as well as neurological 
      disorders. Angiotensin II (Ang II), which interacts with Ang II type 1 receptor 
      (AT(1)-R) in the brain, plays an important role as a neuromodulator in 
      dopaminergic transmission. However, the role of brain RAS in METH-induced 
      behavior is largely unknown. Here, we revealed that repeated METH administration 
      significantly upregulated the expression of AT(1)-R in the striatum of mice, but 
      downregulated dopamine D3 receptor (D3R) expression. A specific AT(1)-R blocker 
      telmisartan, which can penetrate the brain-blood barrier (BBB), or genetic 
      deletion of AT(1)-R was sufficient to attenuate METH-triggered hyperlocomotion in 
      mice. However, intraperitoneal injection of AT(1)-R blocker losartan, which 
      cannot penetrate BBB, failed to attenuate METH-induced behavior. Moreover, 
      intra-striatum re-expression of AT(1) with lentiviral virus expressing AT(1) 
      reversed the weakened locomotor activity of AT(1)(-/-) mice treated with METH. 
      Losartan alleviated METH-induced cytotoxicity in SH-SY5Y cells in vitro, which 
      was accompanied by upregulated expressions of D3R and dopamine transporter. In 
      addition, intraperitoneal injection of perindopril, which is a specific ACE 
      inhibitor and can penetrate BBB, significantly attenuated METH-induced 
      hyperlocomotor activity. Collectively, our results show that blockade of brain 
      RAS attenuates METH-induced hyperlocomotion and neurotoxicity possibly through 
      modulation of D3R expression. Our findings reveal a novel role of Ang II-AT(1)-R 
      in METH-induced hyperlocomotion.
FAU - Jiang, Linhong
AU  - Jiang L
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Zhu, Ruiming
AU  - Zhu R
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Bu, Qian
AU  - Bu Q
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
AD  - Department of Food Science and Technology, College of Light Industry, Textile and 
      Food Engineering, Sichuan University, Chengdu, 610065, China.
FAU - Li, Yan
AU  - Li Y
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Shao, Xue
AU  - Shao X
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Gu, Hui
AU  - Gu H
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Kong, Jueying
AU  - Kong J
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Luo, Li
AU  - Luo L
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Long, Hailei
AU  - Long H
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Guo, Wei
AU  - Guo W
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
AD  - School of Pharmacy, Yantai University, Yantai, 264003, China.
AD  - State Key Laboratory of Long-Acting and Targeting Drug Delivery Technologies, 
      Yantai, 264003, China.
FAU - Tian, Jingwei
AU  - Tian J
AD  - School of Pharmacy, Yantai University, Yantai, 264003, China.
AD  - State Key Laboratory of Long-Acting and Targeting Drug Delivery Technologies, 
      Yantai, 264003, China.
FAU - Zhao, Yinglan
AU  - Zhao Y
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China.
FAU - Cen, Xiaobo
AU  - Cen X
AD  - National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of 
      Biotherapy and Cancer Center, West China Hospital, Sichuan University, and 
      Collaborative Innovation Center for Biotherapy, #1 Keyuan Road 4, Gaopeng Street, 
      High-tech Development Zone, Chengdu, 610041, China. xbcen@scu.edu.cn.
LA  - eng
GR  - 81271467/National Natural Science Foundation of China/International
GR  - 81272459/National Natural Science Foundation of China/International
GR  - 30970938/National Natural Science Foundation of China/International
GR  - 81571301/National Natural Science Foundation of China/International
GR  - 81401105/National Natural Science Foundation of China/International
GR  - YJ201790/Fundamental Research Funds for the central Universities/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neurotherapeutics
JT  - Neurotherapeutics : the journal of the American Society for Experimental 
      NeuroTherapeutics
JID - 101290381
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptors, Dopamine D3)
RN  - 44RAL3456C (Methamphetamine)
RN  - JMS50MPO89 (Losartan)
RN  - U5SYW473RQ (Telmisartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*administration & dosage
MH  - Angiotensin-Converting Enzyme Inhibitors/administration & dosage
MH  - Animals
MH  - Cell Line, Tumor
MH  - Corpus Striatum/drug effects/metabolism/*physiopathology
MH  - Humans
MH  - Hyperkinesis/chemically induced/*physiopathology
MH  - Losartan/administration & dosage
MH  - Male
MH  - Methamphetamine/*administration & dosage/*toxicity
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptor, Angiotensin, Type 1/genetics/*metabolism
MH  - Receptors, Dopamine D3/metabolism
MH  - Renin-Angiotensin System/*drug effects
MH  - Telmisartan/administration & dosage
MH  - Up-Regulation
PMC - PMC5935642
OTO - NOTNLM
OT  - AT1-R
OT  - Angiotensin II
OT  - D3R
OT  - Hyperlocomotion
OT  - Methamphetamine
OT  - Neurotoxicity.
COIS- The authors declare no competing financial interests.
EDAT- 2018/02/22 06:00
MHDA- 2019/03/14 06:00
PMCR- 2019/04/01
CRDT- 2018/02/22 06:00
PHST- 2018/02/22 06:00 [pubmed]
PHST- 2019/03/14 06:00 [medline]
PHST- 2018/02/22 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - S1878-7479(23)01580-5 [pii]
AID - 613 [pii]
AID - 10.1007/s13311-018-0613-8 [doi]
PST - ppublish
SO  - Neurotherapeutics. 2018 Apr;15(2):500-510. doi: 10.1007/s13311-018-0613-8.