PMID- 35892425
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220824
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 12
IP  - 8
DP  - 2022 Jul 26
TI  - A Novel CaMKII Inhibitory Peptide Blocks Relapse to Morphine Seeking by 
      Influencing Synaptic Plasticity in the Nucleus Accumbens Shell.
LID - 10.3390/brainsci12080985 [doi]
LID - 985
AB  - Drugs of abuse cause enduring functional disorders in the brain reward circuits, 
      leading to cravings and compulsive behavior. Although people may rehabilitate by 
      detoxification, there is a high risk of relapse. Therefore, it is crucial to 
      illuminate the mechanisms of relapse and explore the therapeutic strategies for 
      prevention. In this research, by using an animal model of morphine 
      self-administration in rats and a whole-cell patch-clamp in brain slices, we 
      found changes in synaptic plasticity in the nucleus accumbens (NAc) shell were 
      involved in the relapse to morphine-seeking behavior. Compared to the controls, 
      the amplitude of long-term depression (LTD) induced in the medium spiny neurons 
      increased after morphine self-administration was established, recovered after the 
      behavior was extinguished, and increased again during the relapse induced by 
      morphine priming. Intravenous injection of MA, a new peptide obtained by 
      modifying Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitor 
      "myr-AIP", decreased CaMKII activity in the NAc shell and blocked the 
      reinstatement of morphine-seeking behavior without influence on the locomotor 
      activity. Moreover, LTD was absent in the NAc shell of the MA-pretreated rats, 
      whereas it was robust in the saline controls in which morphine-seeking behavior 
      was reinstated. These results indicate that CaMKII regulates morphine-seeking 
      behavior through its involvement in the change of synaptic plasticity in the NAc 
      shell during the relapse, and MA may be of great value in the clinical treatment 
      of relapse to opioid seeking.
FAU - Liu, Zhuo
AU  - Liu Z
AD  - People's Public Security University of China, Beijing 100038, China.
FAU - Zhang, Jianjun
AU  - Zhang J
AUID- ORCID: 0000-0001-7526-7234
AD  - CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing 100101, 
      China.
FAU - Miao, Linqing
AU  - Miao L
AUID- ORCID: 0000-0002-1489-0548
AD  - Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing 
      Institute of Technology, Beijing 100081, China.
FAU - Kong, Qingyao
AU  - Kong Q
AD  - Department of Anesthesia and Critical Care, The University of Chicago, Chicago, 
      IL 60637, USA.
FAU - Liu, Xiaodong
AU  - Liu X
AUID- ORCID: 0000-0001-7424-6829
AD  - Beijing Institute of Chinese Medicine, Beijing University of Chinese Medicine, 
      Beijing 100029, China.
FAU - Yu, Longchuan
AU  - Yu L
AD  - School of Life Sciences, Peking University, Beijing 100871, China.
LA  - eng
GR  - 31871111/National Natural Science Foundation of China/
GR  - 2020088/Youth Innovation Promotion Association CAS/
GR  - 2019004/the Key Laboratory of Technology for Drug Prevention and Control in 
      Zhejiang Police College/
PT  - Journal Article
DEP - 20220726
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC9394410
OTO - NOTNLM
OT  - Ca2+/calmodulin-dependent protein kinase II
OT  - long-term depression
OT  - morphine self-administration
OT  - nucleus accumbens shell
OT  - opioids
OT  - reinstatement
OT  - relapse
OT  - synaptic plasticity
COIS- The authors declare no conflict of interest.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/26
CRDT- 2022/07/27 04:53
PHST- 2022/06/20 00:00 [received]
PHST- 2022/07/12 00:00 [revised]
PHST- 2022/07/23 00:00 [accepted]
PHST- 2022/07/27 04:53 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/26 00:00 [pmc-release]
AID - brainsci12080985 [pii]
AID - brainsci-12-00985 [pii]
AID - 10.3390/brainsci12080985 [doi]
PST - epublish
SO  - Brain Sci. 2022 Jul 26;12(8):985. doi: 10.3390/brainsci12080985.