Altered phosphorylation of GluA1 in the striatum is associated with locomotor sensitization induced by exposure to increasing doses of morphine

Ding, Xuekun; Liang, Jing; Zheng, Xiang; Bai, Yunjing; Liu, Zhengkui; Li, Yingying; Xing, Xiaoli

doi:10.1016/j.ejphar.2013.01.051

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…Although phospho-GluR1/ Ser831 and Ser845 both contribute to AMPA receptor function and play a role in behavioral extinction, they seem to involve different contexts of extinction and did not display concomitant changes (Ding et al 2013;Tao et al 2014). Our current finding that GluR1/Ser845, but not Ser831, phosphorylation enhanced in the VTA along with an increased number of dendritic spines and AMPA insertion during METH-CPP extinction indicates this GluR1 residue-dependent neuroplasticity may involve in extinction learning at the site of VTA.…”

Section: Discussionmentioning

confidence: 50%

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

Chen

2015

Learn. Mem.

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The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning.

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Section: Discussionmentioning

confidence: 50%

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

Chen

2015

Learn. Mem.

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“…To examine the protein expression of MRs and GRs in the DH and the VH, Western blot was used. The basic protocol was similar to previous studies (Ding et al., ; Liang et al., ). Tissue samples were homogenized in 10 volumes of lysis buffer.…”

Section: Methodsmentioning

confidence: 84%

Mineralocorticoid receptors in the ventral hippocampus are involved in extinction memory in rats

et al. 2014

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Fear extinction decreases conditioned fear responses that normally occur when a conditioned stimulus (CS) is repeatedly presented in the absence of an aversive unconditioned stimulus (US), which is the behavioral basis of exposure therapy for posttraumatic stress disorder (PTSD). However, knowledge about the neurobiology of extinction is insufficient. The present study investigated changes in the protein expression of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the dorsal hippocampus (DH)and ventral hippocampus (VH), induced by extinction and return of conditioned fear responses to an auditory signal. Western blot analysis indicated that shock stress enhanced the expression of MRs in only the DH, whereas extinction selectively increased the expression of MRs in the VH. The infusion of MRs antagonist spironolactone in the VH indicated that MRs in the VH did not affect the retrieval of fear and extinction memories, but facilitated the formation of extinction memory. However, no changes in GRs in either the DH or VH were observed in each phase of auditory fear conditioning. These results suggest that MRs in the DH and VH have differential functions in the extinction of auditory fear conditioning. MRs in the DH appear to be related to only stressful experiences, whereas MRs in the VH are involved in extinction formation. The enhancement of MRs in the VH might be necessary to improve PTSD.

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“…It is well known that different types of glutamate receptors play important and specific roles in synaptic transmission and plasticity [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. The AMPA receptor, one of the three types of ionotropic glutamate receptors (iGluRs), is integral to synaptic plasticity [ 22 , 23 , 24 ] and is involved in opioid addiction [ 25 , 26 , 27 , 28 , 29 ]. For example, after a single morphine injection, the mRNA levels of AMPA receptor subunits were significantly reduced three days later but enhanced three weeks later in the NAc core [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Intravenous Injection of GluR2-3Y Inhibits Repeated Morphine-Primed Reinstatement of Drug Seeking in Rats

张

Liu

et al. 2023

Brain Sciences

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Studies have demonstrated that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is essential to drug addiction. In this study, we explored the influence of GluR2-3Y, an interfering peptide to prevent the endocytosis of AMPA receptors containing the GluR2 subunit, on morphine-seeking behavior in the rat self-administration model. After self-administration was established, the rats received intravenous injections of GluR2-3Y during the extinction sessions. There were no significant differences in both active and inactive pokes compared to the control group of rats that received GluR2-3S, indicating that GluR2-3Y has no significant influences on the extinction of morphine self-administration. The other two groups of rats were trained, extinguished, and reinstated by repeated morphine priming (respectively, called Prime 1, Prime 2, and Prime 3). Only one intravenous injection of GluR2-3Y was performed before Prime 1. Compared to the control group, GluR2-3Y did not affect Prime 1, but significantly attenuated the morphine-seeking behavior during repeated morphine-primed reinstatement, indicating an inhibitory after effect of GluR2-3Y on morphine-seeking behavior in rats. The long-term depression (LTD) in the nucleus accumbens (NAc) shell was also assessed. Pretreatment with GluR2-3Y altered the ability of LTD induction to the level of that in the naive group, while pretreatment with GluR2-3S had no effects on LTD. Our results demonstrated that the intravenous injection of GluR2-3Y, to block the endocytosis of AMPA receptors, inhibited the reinstatement of morphine-seeking behavior, which may be induced by modulating the neuronal plasticity in the NAc shell of rats.

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Altered phosphorylation of GluA1 in the striatum is associated with locomotor sensitization induced by exposure to increasing doses of morphine

Cited by 8 publications

References 37 publications

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

Mineralocorticoid receptors in the ventral hippocampus are involved in extinction memory in rats

Intravenous Injection of GluR2-3Y Inhibits Repeated Morphine-Primed Reinstatement of Drug Seeking in Rats

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