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Lee, Jung Won,Kim, Wha Young,Cho, Bo Ram,Vezina, Paul,Kim, Jeong-Hoon Elsevier 2018 Behavioural brain research Vol.337 No.-
<P><B>Abstract</B></P> <P>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 GSK3β 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 GSK3β in these processes, we microinjected S9 peptide, a small synthetic peptide acting as a competitive inhibitor against phosphorylation site of GSK3β, 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 GSK3β may play a major role in mediating these processes.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The nucleus accumbens core is known to mediate cocaine-induced hyper-locomotion. </LI> <LI> Leptin in the nucleus accumbens core disrupts cocaine-induced hyper-locomotion. </LI> <LI> Leptin recovers cocaine-induced decrease of GSK3β phosphorylation. </LI> <LI> GSK3β may mediate leptin’s regulatory role in cocaine-induced hyper-locomotion. </LI> </UL> </P>
Cho, Bo Ram,Yoon, Hyung Shin,Kim, Wha Young,Vezina, Paul,Kim, Jeong-Hoon Lippincott Williams & Wilkins 2017 NeuroReport Vol.28 No.11
<P>Two well-known appetite-regulatory peptides, leptin and cocaine-and amphetamine-regulated transcript (CART), are known to be involved in the brain rewarding pathway. However, it is not yet known how they interact in the nucleus accumbens, an important region mediating the rewarding effects of drugs of abuse. Using the immunoassay method, we found that a microinjection of leptin into the nucleus accumbens core induces an immediate and transient increase of the CART peptide in this site, whereas these effects were inhibited by cocaine. These results expand the role of accumbal leptin to the regulation of the CART peptide and further suggest that possible interaction of these appetite-regulating peptides may be involved in cocainemediated rewarding effects. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.</P>