Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine

Wang, Jun; Sun, Lei; Zhu, Weili; Sun, Yan; Liu, Jianfeng; Lü, Lin; Shi, Jie

doi:10.1007/s00213-011-2461-7

Cited by 12 publications

(10 citation statements)

References 46 publications

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“…Interestingly, Akt/GSK3/mTORC1 pathway is implicated in the reconsolidation of cocaine induced conditioned place preference and contextual memories are erased by GSK3 inhibition [11]. Previous studies suggest that chronic MA exposure decreases the phosphorylation of GSK3β in the ventral M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 tegmental area [12] and acute amphetamine treatment decreases the phosphorylation of Akt/GSK3 pathway in the striatum [13]. Besides, MA inhibits the activity of mTOR in both PC12 and SK-N-SH cells and the phosphorylation of mTOR is protective against MA induced neurotoxicity [14,15].…”

Section: Introductionmentioning

confidence: 99%

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Zhu

Zhang

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Introductionmentioning

confidence: 99%

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Zhu

Zhang

et al. 2015

Biochemical and Biophysical Research Communications

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“…For example, whereas meth-AMPH increased GSK-3β activity in the VTA [40], the inhibition of GSK-3β specifically in the rat NAc core, but not NAc shell, suppressed both meth-AMPH and cocaine-induced locomotor sensitization in rats [42,43]. Similarly, GSK-3β inhibition in the CP of mice resulted in a significant attenuation of the development of cocaine sensitization [81].…”

Section: Glycogen Synthase Kinasementioning

confidence: 99%

“…Although GSK-3 exists as two isoforms, GSK-3α and GSK-3β, the majority of research has focused on GSK-3β as a result of its involvement in neuropsychiatric diseases such as schizophrenia and addiction [40,41,42,79,80,81], as well as neurodegenerative disease [82,83]. GSK-3β is a constitutively active kinase that can be inhibited by its phosphorylation at Ser9 [84].…”

Section: Glycogen Synthase Kinasementioning

confidence: 99%

“…A direct role for GSK-3β in addiction has yet to be evaluated; however, some studies have examined its involvement in psychostimulant-induced locomotor sensitization [40,42,43,81]. For example, whereas meth-AMPH increased GSK-3β activity in the VTA [40], the inhibition of GSK-3β specifically in the rat NAc core, but not NAc shell, suppressed both meth-AMPH and cocaine-induced locomotor sensitization in rats [42,43].…”

Section: Glycogen Synthase Kinasementioning

confidence: 99%

“…CaMKII has been shown to play an integral role in addictive processes [33,34,35,36] and has been linked to both brain-derived neurotrophic factor (BDNF) expression [37] and glycogen synthase kinase 3 (GSK-3) activity [38], two proteins that also play an important role in processes that contribute to drug addiction [39,40,41,42,43]. In addition, phosphorylation by CaMKII is also involved in the functional regulation of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) [44], thus contributing to AMPAR-induced changes in synaptic plasticity that mediate the development of addiction [44,45,46].…”

Section: The Dopamine D1-d2 Receptor Heteromermentioning

confidence: 99%

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Dopamine D<sub>1</sub>-D<sub>2</sub> Receptor Heteromer Regulates Signaling Cascades Involved in Addiction: Potential Relevance to Adolescent Drug Susceptibility

Perreault

O’Dowd

George³

2014

Dev Neurosci

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Adolescence is a developmental period that has been associated with heightened sensitivity to psychostimulant-induced reward, thus placing adolescents at increased risk to develop drug addiction. Although alterations in dopamine-induced synaptic plasticity are perhaps the most critical factor in mediating addiction processes, developmental differences in the cell signaling mechanisms that contribute to synaptic plasticity, and their contribution to adolescent reward sensitivity, has been grossly understudied. The most abundant dopamine receptors, the D₁ and D₂ receptors, as well as the dopamine D₁-D₂ receptor heteromer, exhibit age-dependent and brain region-specific changes in their expression and function and are responsible for regulating cell signaling pathways known to significantly contribute to the neurobiological mechanisms underlying addiction. The D₁-D₂ receptor heteromer, for instance, has been associated with calcium calmodulin kinase IIα, brain-derived neurotrophic factor and glycogen synthase kinase 3 (GSK-3) signaling, three proteins highly implicated in the regulation of glutamate transmission and synaptic plasticity and which regulate addiction to amphetamine, opioids and cocaine. Therefore, in this review the importance of these signaling proteins as potential mediators of addiction susceptibility in adolescence will be highlighted, and the therapeutic potential of the D₁-D₂ receptor heteromer in addiction will be discussed. It is the overall goal of this review to draw attention to the research gap in dopamine-induced cell signaling in the adolescent brain - knowledge that would provide much-needed insights into adolescent addiction vulnerability.

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Increasing methamphetamine doses inhibit glycogen synthase kinase 3β activity by stimulating the insulin signaling pathway in substantia nigra

Valian

Ahmadiani

Dargahi

2018

J of Cellular Biochemistry

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Methamphetamine (MA), a highly abused psychostimulant, exerts neurotoxic effects on the dopaminergic system via several neurotoxicity mechanisms in the long-term administration. Since the effect of MA on the signaling insulin pathway is less studied, the current study was designed to evaluate the effect of escalating an MA regimen on different insulin signaling elements in substantia nigra (SN) and striatum of a rat. Increasing MA doses (1-14 mg/kg) were administrated intraperitoneally twice a day for 14 days in rats. In the control group, normal saline was injected in the same volume. On days 1, 14, 28, and 60 after MA discontinuation, molecular assessments were performed. Insulin receptor (IR) and insulin receptor substrate (IRS) 1 and 2 gene expression were evaluated using real-time polymerase chain reaction, and protein levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt, glycogen synthase kinase 3β (GSK3β), and phospho-GSK3β were measured by the Western blot analysis in SN and striatum. Messenger RNA levels of IR and insulin receptor substrate 2 were increased in SN, 1 day after the last injection. Although no changes were observed in PI3K, phospho-PI3K, Akt, phospho-Akt, and GSK3β levels, increase in the level of inactive form of GSK3β (phosphorylated on serine 9) was indicated in SN on day 28. In striatum, decreases in IR and phospho-Akt were demonstrated, without any change in other elements. Repeated escalating regimen of MA activated the insulin signaling pathway and inhibited GSK3β activity in SN. This response, which did not occur in striatum, may act as an adaptive mechanism to prevent MA-induced neurotoxicity in dopaminergic cell bodies.

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Role of calcineurin in the VTA in rats behaviorally sensitized to methamphetamine

Cited by 12 publications

References 46 publications

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Dopamine D<sub>1</sub>-D<sub>2</sub> Receptor Heteromer Regulates Signaling Cascades Involved in Addiction: Potential Relevance to Adolescent Drug Susceptibility

Increasing methamphetamine doses inhibit glycogen synthase kinase 3β activity by stimulating the insulin signaling pathway in substantia nigra

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