Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization Through the GluN2B-PP2A-AKT Cascade in the Dorsal Striatum of Mice
Abstract Drug addiction can be described as a chronic and relapsing brain disease. Behavioral sensitization is believed to share similar mechanisms with relapse. Our previous studies have demonstrated that ifenprodil could attenuate methamphetamine (METH)-induced behavioral sensitization. However, the mechanism underlying this process has not been fully investigated. Protein phosphatase 2A (PP2A) is a conserved serine/threonine protein phosphatase that has been linked to many neurological diseases; however, there are few reports about PP2A in the context of drug addiction. In this study, we measured the level of phosphorylated (p-) GluN2B (Serine; Ser 1303), PP2A/B (a regulatory subunit of PP2A), and PP2A/C (a catalytic subunit of PP2A) in different brain regions such as the prefrontal cortex (PFc), nucleus accumbens (NAc), dorsal striatum (DS), and hippocampus (Hip). We also used ifenprodil, a selective antagonist of GluN2B to clarify the relationship between GluN2B and PP2A. The results showed that METH increased the level of p-GluN2B (Ser 1303) and PP2A/B in the DS and ifenprodil blocked this increase. We further examined the interaction between PP2A/B and PP2A/C in the DS and found that METH treatment increased the interaction between PP2A/B and PP2A/C, which was also blocked by ifenprodil. Then, we explored the pathway downstream of PP2A in the DS and found that p-AKT (Threonine; Thr 308) but not p-AKT (Ser 473) was dephosphorylated by PP2A. Taken together, these results indicated that the GluN2B-PP2A-AKT cascade was involved in METH-induced behavioral sensitization..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Neurochemical research - 45(2020), 4 vom: 24. Jan., Seite 891-901 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Gang [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| BKL: | |
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| Themen: |
-Methyl-D-aspartate receptors |
| doi: |
10.1007/s11064-020-02966-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract Drug addiction can be described as a chronic and relapsing brain disease. Behavioral sensitization is believed to share similar mechanisms with relapse. Our previous studies have demonstrated that ifenprodil could attenuate methamphetamine (METH)-induced behavioral sensitization. However, the mechanism underlying this process has not been fully investigated. Protein phosphatase 2A (PP2A) is a conserved serine/threonine protein phosphatase that has been linked to many neurological diseases; however, there are few reports about PP2A in the context of drug addiction. In this study, we measured the level of phosphorylated (p-) GluN2B (Serine; Ser 1303), PP2A/B (a regulatory subunit of PP2A), and PP2A/C (a catalytic subunit of PP2A) in different brain regions such as the prefrontal cortex (PFc), nucleus accumbens (NAc), dorsal striatum (DS), and hippocampus (Hip). We also used ifenprodil, a selective antagonist of GluN2B to clarify the relationship between GluN2B and PP2A. The results showed that METH increased the level of p-GluN2B (Ser 1303) and PP2A/B in the DS and ifenprodil blocked this increase. We further examined the interaction between PP2A/B and PP2A/C in the DS and found that METH treatment increased the interaction between PP2A/B and PP2A/C, which was also blocked by ifenprodil. Then, we explored the pathway downstream of PP2A in the DS and found that p-AKT (Threonine; Thr 308) but not p-AKT (Ser 473) was dephosphorylated by PP2A. Taken together, these results indicated that the GluN2B-PP2A-AKT cascade was involved in METH-induced behavioral sensitization. | ||
| 650 | 4 | |a Behavioral sensitization |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Methamphetamine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Ifenprodil |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a -Methyl-D-aspartate receptors |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Li, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Qiao, Chuchu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xinshe |e verfasserin |4 aut | |
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