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Leptin in the nucleus accumbens core disrupts acute cocaine effects: Implications for GSK3beta connections

Authors
 Jung Won Lee  ;  Wha Young Kim  ;  Bo Ram Cho  ;  Paul Vezina  ;  Jeong-Hoon Kim 
Citation
 BEHAVIOURAL BRAIN RESEARCH, Vol.337 : 46-52, 2018 
Journal Title
 BEHAVIOURAL BRAIN RESEARCH 
ISSN
 0166-4328 
Issue Date
2018
MeSH
Analysis of Variance ; Local/*pharmacology Anesthetics ; Animals ; Cocaine/*pharmacology ; Drug Dose-Response Relationship ; Female ; Enzymologic/drug effects Gene Expression Regulation ; Glycogen Synthase Kinase 3 beta/*metabolism ; Leptin/*pharmacology ; Locomotion/drug effects ; Male ; Nucleus Accumbens/*drug effects ; Phosphorylation/drug effects ; Rats ; Sprague-Dawley Rats ; STAT3 Transcription Factor/metabolism
Keywords
Cocaine ; GSK3beta ; Leptin ; Locomotor activity ; Nucleus accumbens
Abstract
An adipose-derived peptide hormone, leptin, has a regulatory role in reward-related behaviors produced by drugs of abuse. Although it is known that leptin modulates mesolimbic dopaminergic pathways, little is known about its direct role in the nucleus accumbens (NAcc). In the present study, we measured acute cocaine-induced locomotor activity in the rat and the phosphorylation levels of GSK3beta after bilateral microinjections of leptin into the NAcc core. Interestingly, leptin in the NAcc core significantly disrupts acute cocaine's effects on both locomotor activity and signaling molecules. In order to further confirm the role of GSK3beta in these processes, we microinjected S9 peptide, a small synthetic peptide acting as a competitive inhibitor against phosphorylation site of GSK3beta, followed by leptin co-microinjection, and found that leptin's effects on cocaine were all nullified. These results indicate that leptin in the NAcc core has a negative regulatory role in acute cocaine' effects, and suggest that GSK3beta may play a major role in mediating these processes.
Full Text
https://www.sciencedirect.com/science/article/pii/S0166432817313980
DOI
10.1016/j.bbr.2017.09.049
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jeong Hoon(김정훈) ORCID logo https://orcid.org/0000-0001-7095-3729
Kim, Wha Young(김화영) ORCID logo https://orcid.org/0000-0003-1744-7012
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/161831
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