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Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-Reinstated Drug Seeking
Shen, Hao-wei1,2; Gipson, Cassandra D.1; Huits, Martijn3; Kalivas, Peter W.1
关键词cocaine self-administration synaptic plasticity reinstatement prefrontal cortex accumbens core
刊名NEUROPSYCHOPHARMACOLOGY
2014-04-01
DOI10.1038/npp.2013.318
39期:5页:1169-1177
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
资助者National Institutes of Health ; National Institutes of Health
研究领域[WOS]Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]CALCIUM-PERMEABLE AMPA ; RECEPTOR STIMULATION INCREASES ; ANTERIOR CINGULATE CORTEX ; LONG-TERM POTENTIATION ; PREFRONTAL CORTEX ; DENDRITIC SPINES ; IN-VIVO ; STRUCTURAL PLASTICITY ; GLUTAMATE RECEPTORS ; SURFACE EXPRESSION
英文摘要

Addictive drug use causes long-lasting changes in synaptic strength and dendritic spine morphology in the nucleus accumbens that might underlie the vulnerability to relapse. Although activity in mesocorticolimbic circuitry is required for reinstating cocaine seeking, its role in reinstatement-associated synaptic plasticity is not well characterized. Using rats extinguished from cocaine self-administration, we found potentiated synaptic strength (assessed as the AMPA/NMDA current amplitude ratio) and increased spine head diameter in medium spiny neurons in the accumbens core (NAcore). The basal changes in synaptic strength and morphology in cocaine-extinguished animals were further augmented during cocaine-induced reinstatement. Two NAcore afferents contributing to cocaine reinstatement are glutamatergic inputs from the prelimbic prefrontal cortex (PL) and dopamine from the ventral tegmental area (VIA). Pharmacological inhibition of either PL or VIA prevented cocaine-primed reinstatement. However, inhibiting the PL further potentiated AMPA/NMDA and spine head diameter, while inactivating the VIA or the combined systemic administration of dopamine D1 and D2 antagonists prevented the increase in AMPA/NMDA and spine diameter induced by cocaine priming. These data indicate that neuronal activity in the VTA and associated dopamine receptor stimulation is necessary for the synaptic potentiation in the NAcore during cocaine-induced reinstatement. Although activity in the PL was necessary for reinstatement, it inhibited synaptic potentiation initiated by an acute cocaine injection. Thus, although the PL and VTA differentially regulate the direction of synaptic plasticity induced by a cocaine-priming injection, coordinated synaptic potentiation by both NAcore afferents is necessary for cocaine-induced relapse.

语种英语
所属项目编号DA007288 ; DA03906 ; DA012513 ; DA015369
资助者National Institutes of Health ; National Institutes of Health
WOS记录号WOS:000332918100013
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64345
专题中国药物依赖性研究所
作者单位1.Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA
2.Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China
3.Vrije Univ Amsterdam, Dept Neurosci, Amsterdam, Netherlands
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GB/T 7714
Shen, Hao-wei,Gipson, Cassandra D.,Huits, Martijn,et al. Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-Reinstated Drug Seeking[J]. NEUROPSYCHOPHARMACOLOGY,2014,39(5):1169-1177.
APA Shen, Hao-wei,Gipson, Cassandra D.,Huits, Martijn,&Kalivas, Peter W..(2014).Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-Reinstated Drug Seeking.NEUROPSYCHOPHARMACOLOGY,39(5),1169-1177.
MLA Shen, Hao-wei,et al."Prelimbic Cortex and Ventral Tegmental Area Modulate Synaptic Plasticity Differentially in Nucleus Accumbens During Cocaine-Reinstated Drug Seeking".NEUROPSYCHOPHARMACOLOGY 39.5(2014):1169-1177.
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