PMID- 24154664
OWN - NLM
STAT- MEDLINE
DCOM- 20141010
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 39
IP  - 4
DP  - 2014 Mar
TI  - CaMKII activity in the ventral tegmental area gates cocaine-induced synaptic 
      plasticity in the nucleus accumbens.
PG  - 989-99
LID - 10.1038/npp.2013.299 [doi]
AB  - Addictive drugs such as cocaine induce synaptic plasticity in discrete regions of 
      the reward circuit. The aim of the present study is to investigate whether 
      cocaine-evoked synaptic plasticity in the ventral tegmental area (VTA) and 
      nucleus accumbens (NAc) is causally linked. Ca(2+)/calmodulin-dependent protein 
      kinase II (CaMKII) is a central regulator of long-term synaptic plasticity, 
      learning, and drug addiction. We examined whether blocking CaMKII activity in the 
      VTA affected cocaine conditioned place preference (CPP) and cocaine-evoked 
      synaptic plasticity in its target brain region, the NAc. TatCN21 is a CaMKII 
      inhibitory peptide that blocks both stimulated and autonomous CaMKII activity 
      with high selectivity. We report that intra-VTA microinjections of tatCN21 before 
      cocaine conditioning blocked the acquisition of cocaine CPP, whereas intra-VTA 
      microinjections of tatCN21 before saline conditioning did not significantly 
      affect cocaine CPP, suggesting that the CaMKII inhibitor blocks cocaine CPP 
      through selective disruption of cocaine-cue-associated learning. Intra-VTA 
      tatCN21 before cocaine conditioning blocked cocaine-evoked depression of 
      excitatory synaptic transmission in the shell of the NAc slices ex vivo. In 
      contrast, intra-VTA microinjection of tatCN21 just before the CPP test did not 
      affect the expression of cocaine CPP and cocaine-induced synaptic plasticity in 
      the NAc shell. These results suggest that CaMKII activity in the VTA governs 
      cocaine-evoked synaptic plasticity in the NAc during the time window of cocaine 
      conditioning.
FAU - Liu, Xiaojie
AU  - Liu X
AD  - 1] Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA [2] Department of Physiology, Shanxi Medical University, 
      Taiyuan, China.
FAU - Liu, Yong
AU  - Liu Y
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA.
FAU - Zhong, Peng
AU  - Zhong P
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA.
FAU - Wilkinson, Brianna
AU  - Wilkinson B
AD  - Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA.
FAU - Qi, Jinshun
AU  - Qi J
AD  - Department of Physiology, Shanxi Medical University, Taiyuan, China.
FAU - Olsen, Christopher M
AU  - Olsen CM
AD  - 1] Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA [2] Neuroscience Research Center, Medical College of 
      Wisconsin, Milwaukee, WI, USA.
FAU - Bayer, K Ulrich
AU  - Bayer KU
AD  - Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA.
FAU - Liu, Qing-song
AU  - Liu QS
AD  - 1] Department of Pharmacology and Toxicology, Medical College of Wisconsin, 
      Milwaukee, WI, USA [2] Neuroscience Research Center, Medical College of 
      Wisconsin, Milwaukee, WI, USA.
LA  - eng
GR  - R01NS081248/NS/NINDS NIH HHS/United States
GR  - UL1RR031973/RR/NCRR NIH HHS/United States
GR  - R01 DA024741/DA/NIDA NIH HHS/United States
GR  - R21 DA036300/DA/NIDA NIH HHS/United States
GR  - R01 NS081248/NS/NINDS NIH HHS/United States
GR  - UL1 RR031973/RR/NCRR NIH HHS/United States
GR  - R00 DA026994/DA/NIDA NIH HHS/United States
GR  - R21 MH095921/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131024
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Cocaine/*administration & dosage
MH  - Conditioning, Operant/drug effects/physiology
MH  - Dopamine Uptake Inhibitors/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Male
MH  - N-Methylaspartate/pharmacology
MH  - Neural Pathways/drug effects/physiology
MH  - Neuronal Plasticity/*drug effects/physiology
MH  - Nucleus Accumbens/cytology/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Time Factors
MH  - Ventral Tegmental Area/drug effects/*enzymology
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
PMC - PMC3924533
EDAT- 2013/10/25 06:00
MHDA- 2014/10/11 06:00
PMCR- 2015/03/01
CRDT- 2013/10/25 06:00
PHST- 2013/09/22 00:00 [received]
PHST- 2013/10/17 00:00 [revised]
PHST- 2013/10/18 00:00 [accepted]
PHST- 2013/10/25 06:00 [entrez]
PHST- 2013/10/25 06:00 [pubmed]
PHST- 2014/10/11 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - npp2013299 [pii]
AID - 10.1038/npp.2013.299 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2014 Mar;39(4):989-99. doi: 10.1038/npp.2013.299. Epub 
      2013 Oct 24.