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http://dx.doi.org/10.4196/kjpp.2022.26.1.59

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

Shin, Joong-Keun (Departments of Physiology, Yonsei University College of Medicine)
Kim, Wha Young (Departments of Physiology, Yonsei University College of Medicine)
Rim, Haeun (Departments of Medical Sciences, Yonsei University College of Medicine)
Kim, Jeong-Hoon (Departments of Physiology, Yonsei University College of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.26, no.1, 2022 , pp. 59-65 More about this Journal
Abstract
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;
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1 Kalivas PW, Stewart J. Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev. 1991;16:223-244.   DOI
2 Hyman SE. Addiction to cocaine and amphetamine. Neuron. 1996;16:901-904.   DOI
3 Goto Y, Grace AA. Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci. 2008;31:552-558.   DOI
4 Beaulieu JM, Gainetdinov RR, Caron MG. The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci. 2007;28:166-172.   DOI
5 Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol. 2009;49:327-347.   DOI
6 Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, Pearl LH. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell. 2001;105:721-732.   DOI
7 Frame S, Cohen P, Biondi RM. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell. 2001;7:1321-1327.   DOI
8 Robbins TW, Cador M, Taylor JR, Everitt BJ. Limbic-striatal interactions in reward-related processes. Neurosci Biobehav Rev. 1989;13:155-162.   DOI
9 Miller JS, Tallarida RJ, Unterwald EM. Cocaine-induced hyperactivity and sensitization are dependent on GSK3. Neuropharmacology. 2009;56:1116-1123.   DOI
10 Xu CM, Wang J, Wu P, Xue YX, Zhu WL, Li QQ, Zhai HF, Shi J, Lu L. Glycogen synthase kinase 3β in the nucleus accumbens core is critical for methamphetamine-induced behavioral sensitization. J Neurochem. 2011;118:126-139.   DOI
11 Fuchs RA, Ramirez DR, Bell GH. Nucleus accumbens shell and core involvement in drug context-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl). 2008;200:545-556.   DOI
12 Chaudhri N, Sahuque LL, Schairer WW, Janak PH. Separable roles of the nucleus accumbens core and shell in context- and cueinduced alcohol-seeking. Neuropsychopharmacology. 2010;35:783-791.   DOI
13 Singer BF, Forneris J, Vezina P. Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamineinduced locomotor conditioning. Behav Brain Res. 2014;275:96-100.   DOI
14 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. Boston: Elsevier Academic Press; 2004.
15 Beaulieu JM, Del'guidice T, Sotnikova TD, Lemasson M, Gainetdinov RR. Beyond cAMP: the regulation of Akt and GSK3 by dopamine receptors. Front Mol Neurosci. 2011;4:38.   DOI
16 Miller JS, Barr JL, Harper LJ, Poole RL, Gould TJ, Unterwald EM. The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice. PLoS One. 2014;9:e88026.   DOI
17 Wickens RH, Quartarone SE, Beninger RJ. Inhibition of glycogen synthase kinase-3 by SB 216763 affects acquisition at lower doses than expression of amphetamine-conditioned place preference in rats. Behav Pharmacol. 2017;28:262-271.   DOI
18 Franklin TR, Druhan JP. Involvement of the nucleus accumbens and medial prefrontal cortex in the expression of conditioned hyperactivity to a cocaine-associated environment in rats. Neuropsychopharmacology. 2000;23:633-644.   DOI
19 Kim WY, Vezina P, Kim JH. Blockade of group II, but not group I, mGluRs in the rat nucleus accumbens inhibits the expression of conditioned hyperactivity in an amphetamine-associated environment. Behav Brain Res. 2008;191:62-66.   DOI
20 Bossert JM, Poles GC, Wihbey KA, Koya E, Shaham Y. Differential effects of blockade of dopamine D1-family receptors in nucleus accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues. J Neurosci. 2007;27:12655-12663.   DOI
21 Leroy K, Brion JP. Developmental expression and localization of glycogen synthase kinase-3beta in rat brain. J Chem Neuroanat . 1999;16:279-293.   DOI
22 Xie X, Lasseter HC, Ramirez DR, Ponds KL, Wells AM, Fuchs RA. Subregion-specific role of glutamate receptors in the nucleus accumbens on drug context-induced reinstatement of cocaine-seeking behavior in rats. Addict Biol. 2012;17:287-299.   DOI
23 Singer BF, Bubula N, Li D, Przybycien-Szymanska MM, Bindokas VP, Vezina P. Drug-paired contextual stimuli increase dendritic spine dynamics in select nucleus accumbens neurons. Neuropsychopharmacology. 2016;41:2178-2187.   DOI
24 Beaulieu JM, Caron MG. Looking at lithium: molecular moods and complex behaviour. Mol Interv. 2008;8:230-241.   DOI
25 Kim WY, Cai WT, Jang JK, Kim JH. Ezrin-radixin-moesin proteins are regulated by Akt-GSK3β signaling in the rat nucleus accumbens core. Korean J Physiol Pharmacol. 2020;24:121-126.   DOI
26 Cruz FC, Babin KR, Leao RM, Goldart EM, Bossert JM, Shaham Y, Hope BT. Role of nucleus accumbens shell neuronal ensembles in context-induced reinstatement of cocaine-seeking. J Neurosci. 2014;34:7437-7446.   DOI
27 Domjan M. Pavlovian conditioning: a functional perspective. Annu Rev Psychol. 2005;56:179-206.   DOI
28 Jongen-Relo AL, Voorn P, Groenewegen HJ. Immunohistochemical characterization of the shell and core territories of the nucleus accumbens in the rat. Eur J Neurosci. 1994;6:1255-1264.   DOI
29 Enman NM, Unterwald EM. Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization in the mouse. Behav Brain Res. 2012;231:217-225.   DOI
30 Kim WY, Jang JK, Lee JW, Jang H, Kim JH. Decrease of GSK3β phosphorylation in the rat nucleus accumbens core enhances cocaine-induced hyper-locomotor activity. J Neurochem. 2013;125:642-648.   DOI
31 Zahm DS. An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbens. Neurosci Biobehav Rev. 2000;24:85-105.   DOI
32 Meredith GE, Baldo BA, Andrezjewski ME, Kelley AE. The structural basis for mapping behavior onto the ventral striatum and its subdivisions. Brain Struct Funct. 2008;213:17-27.   DOI
33 Stewart J, Vezina P. Conditioning and behavioral sensitization. In: Kalivas PW, Barnes CD, editors. Sensitization in the nervous system. Caldwell: Telford Press; 1988. p.207-224.
34 O'Brien CP, Childress AR, McLellan AT, Ehrman R. Classical conditioning in drug-dependent humans. Ann N Y Acad Sci. 1992;654:400-415.   DOI
35 Xu CM, Wang J, Wu P, Zhu WL, Li QQ, Xue YX, Zhai HF, Shi J, Lu L. Glycogen synthase kinase 3beta in the nucleus accumbens core mediates cocaine-induced behavioral sensitization. J Neurochem. 2009;111:1357-1368.   DOI
36 Shi X, Barr JL, von Weltin E, Wolsh C, Unterwald EM. Differential roles of accumbal GSK3β in cocaine versus morphine-induced place preference, U50,488H-induced place aversion, and object memory. J Pharmacol Exp Ther. 2019;371:339-347.   DOI
37 Shi X, Miller JS, Harper LJ, Poole RL, Gould TJ, Unterwald EM. Reactivation of cocaine reward memory engages the Akt/GSK3/ mTOR signaling pathway and can be disrupted by GSK3 inhibition. Psychopharmacology (Berl). 2014;231:3109-3118.   DOI
38 Yoon HS, Kim WY, Kim JH. Microinjection of CART peptide 55-102 into the nucleus accumbens core inhibits the expression of conditioned hyperactivity in a cocaine-associated environment. Behav Brain Res. 2010;207:169-173.   DOI
39 Tzschentke TM. Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol. 2007;12:227-462.   DOI