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Ifenprodil Attenuates Methamphetamine-Induced Behavioral Sensitization Through the GluN2B-PP2A-AKT Cascade in the Dorsal Striatum of Mice.
- Source :
- Neurochemical Research; Apr2020, Vol. 45 Issue 4, p891-901, 11p
- Publication Year :
- 2020
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03643190
- Volume :
- 45
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Neurochemical Research
- Publication Type :
- Academic Journal
- Accession number :
- 142293720
- Full Text :
- https://doi.org/10.1007/s11064-020-02966-8