Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen
Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved..
Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-d-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and ΔFosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and ΔFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-ΔFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:335 |
|---|---|
| Enthalten in: |
Neuroscience - 335(2016) vom: 29. Okt., Seite 20-9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Li, Lu [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.12.2017 Date Revised 21.12.2017 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.neuroscience.2016.08.022 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM263608344 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM263608344 | ||
| 003 | DE-627 | ||
| 005 | 20231224204254.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.neuroscience.2016.08.022 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0878.xml |
| 035 | |a (DE-627)NLM263608344 | ||
| 035 | |a (NLM)27544406 | ||
| 035 | |a (PII)S0306-4522(16)30395-5 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Li, Lu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ifenprodil attenuates the acquisition and expression of methamphetamine-induced behavioral sensitization and activation of Ras-ERK1/2 cascade in the caudate putamen |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.12.2017 | ||
| 500 | |a Date Revised 21.12.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a Chronic discontinuous use of many psychomotor stimulants leads to behavioral sensitization and, owing to it shares common mechanisms with relapse, most researchers use its animal model to explore the neurobiological mechanisms of addiction. Recent studies have proved that N-methyl-d-aspartate receptors (NMDARs) are implicated in psychomotor stimulant-induced behavioral sensitization. However, the function of GluN2B-containing NMDARs and their potential downstream cascade(s) in the acquisition and expression of behavioral sensitization to methamphetamine (METH) have not been explored. In this study, 2.5, 5, and 10mg/kg ifenprodil, the specific inhibitor of GluN2B, was used to explore the function of these receptors in distinct phases of behavioral sensitization to METH in mice. Then, using western blot, Ras, pERK1/2/ERK1/2, and ΔFosB levels in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were detected. Behavioral results showed that low-dose ifenprodil attenuated the acquisition and expression of behavioral sensitization to METH significantly. Western blot analysis revealed that pre-injection of low-dose ifenprodil in the acquisition markedly attenuated METH-induced ascent of Ras, pERK1/2/ERK1/2, and ΔFosB protein levels in the CPu. However, pre-treatment in the expression only affected the alterations of Ras and pERK1/2/ERK1/2 levels in the CPu. Moreover, chronic METH administration increased pERK1/2/ERK1/2 level in the NAc. In conclusion, GluN2B-containing NMDARs contribute to both the acquisition and expression of behavioral sensitization to METH in mice. Furthermore, the acquisition phase might be mediated by the Ras-ERK1/2-ΔFosB cascade in the CPu while the expression phase may be regulated by the Ras-ERK1/2 cascade in the CPu | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a N-methyl-d-aspartate receptor | |
| 650 | 4 | |a behavioral sensitization | |
| 650 | 4 | |a caudate putamen | |
| 650 | 4 | |a ifenprodil | |
| 650 | 4 | |a methamphetamine | |
| 650 | 4 | |a nucleus accumbens | |
| 650 | 7 | |a Central Nervous System Stimulants |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a Receptors, N-Methyl-D-Aspartate |2 NLM | |
| 650 | 7 | |a Methamphetamine |2 NLM | |
| 650 | 7 | |a 44RAL3456C |2 NLM | |
| 650 | 7 | |a ifenprodil |2 NLM | |
| 650 | 7 | |a R8OE3P6O5S |2 NLM | |
| 700 | 1 | |a Qiao, Chuchu |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xinshe |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Neuroscience |d 1976 |g 335(2016) vom: 29. Okt., Seite 20-9 |w (DE-627)NLM000132403 |x 1873-7544 |7 nnns |
| 773 | 1 | 8 | |g volume:335 |g year:2016 |g day:29 |g month:10 |g pages:20-9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.neuroscience.2016.08.022 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 335 |j 2016 |b 29 |c 10 |h 20-9 | ||