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Behav Brain Res. 2018 Jan 30;337:46-52. doi: 10.1016/j.bbr.2017.09.049. Epub 2017 Sep 28.

Leptin in the nucleus accumbens core disrupts acute cocaine effects: Implications for GSK3β connections.

Author information

1
Department of Physiology, Brain Korea 21 Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.
2
Department of Psychiatry, The University of Chicago, Chicago, IL 60637, USA.
3
Department of Physiology, Brain Korea 21 Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, South Korea. Electronic address: jkim1@yuhs.ac.

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 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.

KEYWORDS:

Cocaine; GSK3β; Leptin; Locomotor activity; Nucleus accumbens

PMID:
28964909
DOI:
10.1016/j.bbr.2017.09.049
[Indexed for MEDLINE]

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