d-Serine in the nucleus accumbens region modulates behavioral sensitization and extinction of conditioned place preference

Liu, Zhiqiang; Gu, Xun-Hu; Yang, Yuan-Jian; Yin, Xiaoping; Xu, Lijun; Wang, Wei

doi:10.1016/j.pbb.2016.02.002

Cited by 20 publications

(13 citation statements)

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“…When accumbal LTD is blocked, this updating cannot occur. This idea is supported by evidence that restoring plasticity lost following cocaine administration dampens addictive phenotypes, including reinstatement (Liu et al, 2016; Moussawi et al, 2009). …”

Section: Discussionmentioning

confidence: 89%

Disrupting GluA2 phosphorylation potentiates reinstatement of cocaine seeking

et al. 2016

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Addiction is associated with changes in synaptic plasticity mediated, in part, by alterations in the trafficking and stabilization of AMPA receptors at synapses within the nucleus accumbens. Exposure to cocaine can lead to protein kinase C–mediated phosphorylation of GluA2 AMPA subunits and this phosphorylation event leads to the internalization of GluA2-containing AMPARs, which are calcium-impermeable. However, it is not clear whether this internalization is necessary for the expression of addictive phenotypes. Utilizing a mouse with a point mutation within the GluA2 subunit c-terminus, the current study demonstrates that disrupting PKC-mediated GluA2 phosphorylation potentiates reinstatement of both cue-induced cocaine seeking and cocaine conditioned reward without affecting operant learning, food self-administration or cocaine sensitization. Electrophysiological recordings revealed increased GluA2-mediated AMPA transmission as evidenced by increased sEPSC amplitude without any changes in sEPSC frequency or rectification. In support of this increase in GluA2 activity mediating the augmented cocaine reinstatement, we found that accumbal overexpression of GluA2 recapitulated this behavioral effect in wildtype mice while not altering reinstatement behavior in the GluA2 K882A knock-in mice. In addition, disrupting GluA2 phosphorylation was associated with blunted long-term depression in the nucleus accumbens, mimicking the anaplasticity seen following cocaine self-administration. Taken together these results indicate that disrupting GluA2 phosphorylation and increasing GluA2-mediated transmission in the nucleus accumbens leads to increased vulnerability to cocaine relapse. Further, these results indicate that modulating GluA2-containing AMPAR trafficking can contribute to addictive phenotypes in the absence of alterations in GluA2-lacking receptors. These results highlight the GluA2 phosphorylation site as a novel target for the development of cocaine addiction therapeutics.

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Section: Discussionmentioning

confidence: 89%

Disrupting GluA2 phosphorylation potentiates reinstatement of cocaine seeking

et al. 2016

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“…Consistently, cocaine treatment leads to reduced D-serine levels in the NAc, which could explain the reduced NMDAR-dependent synaptic plasticity associated with cocaine treatment (both LTP and LTD 119,120 ). In keeping, exogenous D-serine treatment reverts the impaired plasticity and reduces a number of behavioral manifestations associated to cocaine addiction, including cocaine-induced place preference 121,122 , reinstatement of cocaine self-administration (relapse) 123 and locomotor sensitization to cocaine 120,121 . Furthermore, the fact that D-serine treatment can reduce compulsive alcohol intake 124 and that D-serine participates in the mechanisms of morphine addiction 125 suggests a role for altered D-serine signaling in the establishment of addictive behavior at large.…”

Section: Astrocytic Control Of Cognitive Function Goes Awry In Patholmentioning

confidence: 97%

Astrocyte function from information processing to cognition and cognitive impairment

2019

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Astrocytes serve important roles that affect recruitment and function of neurons at the local and network levels. Here we review the contributions of astrocyte signaling to synaptic plasticity, neuronal network oscillations and memory function. The roles played by astrocytes are not fully understood, but astrocytes seem to contribute to memory consolidation and to mediate the effects of vigilance and arousal on memory performance. Understanding the role of astrocytes in cognitive processes may also advance our understanding of how these processes go awry in pathological conditions. Indeed, abnormal astrocytic signaling can cause or contribute to synaptic and network imbalances, leading to cognitive impairment. We discuss evidence for this from animal models of Alzheimer's disease and multiple sclerosis, and from animal studies of sleep deprivation and drug abuse and addiction. Understanding the emerging roles of astrocytes in cognitive function and dysfunction will open up a large array of new therapeutic opportunities.

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“…Recently, research interests are emerging on pharmacological modulation of the NMDA receptor glycine site during extinction of drug reward memory. The NMDA receptor glycine site full agonist d ‐serine and the partial agonist d ‐cycloserine both have the ability to facilitate extinction and reduce the subsequent reinstatement of drug reward memory (Botreau et al ., ; Paolone et al ., ; Lu et al ., ; Hammond et al ., ; Kiefer et al ., ; Liu et al ., ; see Myers & Carlezon, ; for review). Moreover, microinjection of a CB1 receptor antagonist into the NAc before daily test sessions (extinction) facilitated the extinction and decreased the reinstatement after extinction of morphine CPP (Khaleghzadeh‐Ahangar & Haghparast, ).…”

Section: Pharmacological Modulation Of Extinction Of Drug Reward Memorymentioning

confidence: 99%

Modulating reconsolidation and extinction to regulate drug reward memory

Liu

Tian

2018

Eur J of Neuroscience

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Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug-associated cues could result in reconsolidation, a hypothetical process during which original memory could be updated. In contrast, longer exposure times to drug-associated cues could trigger extinction, a process that decreases the conditioned responding. In this review, we discuss the pharmacological and non-pharmacological manipulations on the reconsolidation and extinction that could be used to interfere with drug reward memories. Pharmacological agents such as β-adrenergic receptor antagonist propranolol can interfere with reconsolidation to disrupt drug reward memory. Pharmacological agents such as the NMDA receptor glycine site agonists d-cycloserine and d-serine can facilitate extinction and then attenuate the expression of drug reward memory. Besides pharmacological interventions, drug-free behavioral approaches by utilizing the reconsolidation and extinction, such as 'post-retrieval extinction' and 'UCS-retrieval extinction', are also effective to erase or inhibit the recall of drug reward memory. Taken together, pharmacological modulation and non-pharmacological modulation of reconsolidation and extinction are promising approaches to regulate drug reward memory and prevent relapse.

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d-Serine in the nucleus accumbens region modulates behavioral sensitization and extinction of conditioned place preference

Cited by 20 publications

References 50 publications

Disrupting GluA2 phosphorylation potentiates reinstatement of cocaine seeking

Disrupting GluA2 phosphorylation potentiates reinstatement of cocaine seeking

Astrocyte function from information processing to cognition and cognitive impairment

Modulating reconsolidation and extinction to regulate drug reward memory

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