pISSN 1226-4512 eISSN 2093-3827


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Original Article

Korean J Physiol Pharmacol 2022; 26(1): 59-65

Published online January 1, 2022 https://doi.org/10.4196/kjpp.2022.26.1.59

Copyright © Korean J Physiol Pharmacol.

Decrease of glycogen synthase kinase 3β phosphorylation in the rat nucleus accumbens shell is necessary for amphetamine-induced conditioned locomotor activity

Joong-Keun Shin1,#,†, Wha Young Kim1,#, Haeun Rim2, and Jeong-Hoon Kim1,*

Departments of 1Physiology and 2Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea

Correspondence to:Jeong-Hoon Kim
E-mail: jkim1@yuhs.ac

#These authors contributed equally to this work.
Current address: ILC Dover, 1003 Bukit Merah Central, Singapore 159836

Received: November 23, 2021; Revised: December 8, 2021; Accepted: December 8, 2021

This is an Open Access journal distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Phosphorylation levels of glycogen synthase kinase 3β (GSK3β) negatively correlated with psychomotor stimulant-induced locomotor activity. Locomotor sensitization induced by psychomotor stimulants was previously shown to selectively accompany the decrease of GSK3β phosphorylation in the nucleus accumbens (NAcc) core, suggesting that intact GSK3β activity in this region is necessary for psychomotor stimulants to produce locomotor sensitization. Similarly, GSK3β in the NAcc was also implicated in mediating the conditioned effects formed by the associations of psychomotor stimulants. However, it remains undetermined whether GSK3β plays a differential role in the two sub-regions (core and shell) of the NAcc in the expression of drug-conditioned behaviors. In the present study, we found that GSK3β phosphorylation was significantly lower in the NAcc shell obtained from rats expressing amphetamine (AMPH)-induced conditioned locomotor activity. Further, we demonstrated that these effects were normalized by treatment with lithium chloride, a GSK3β inhibitor. These results suggest that the behavior produced by AMPH itself and a conditioned behavior formed by associations with AMPH are differentially mediated by the two sub-regions of the NAcc.

Keywords: Amphetamine, Classical conditioning, GSK3beta, Lithium chloride, Nucleus accumbens