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不同可卡因戒断条件下大鼠脑结构中 NMDA 受体亚单位(GluN1 和 GluN2A)的调节。

The NMDA Receptor Subunit (GluN1 and GluN2A) Modulation Following Different Conditions of Cocaine Abstinence in Rat Brain Structures.

机构信息

Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Smętna 12, 31-343, Kraków, PL, Poland.

Department of Internal Medicine, Jagiellonian University Medical College, Skawińska 8, 31-066, Kraków, PL, Poland.

出版信息

Neurotox Res. 2021 Jun;39(3):556-565. doi: 10.1007/s12640-021-00350-0. Epub 2021 Mar 24.

Abstract

Different neuronal alterations within glutamatergic system seem to be crucial for developing of cocaine-seeking behavior. Cocaine exposure provokes a modulation of the NMDA receptor subunit expression in rodents, which probably contributes to cocaine-induced behavioral alterations. The aim of this study was to examine the composition of the NMDA receptor subunits in the brain structures in rats with the history of cocaine self-administration after cocaine abstinence (i) in an enriched environment, (ii) in an isolated condition, (iii) with extinction training, or (iv) without instrumental task, as well as the Grin1 (encoding GluN1) and Grin2A (encoding GluN2A) gene expression were evaluated after 10-day extinction training in rat brain structures. In the present study, we observed changes only following cocaine abstinence with extinction training, when the increased GluN2A subunit levels were seen in the postsynaptic density fraction but not in the whole homogenate of the prelimbic cortex (PLC) and dorsal hippocampus (dHIP) in rats previously self-administered cocaine. At the same time, extinction training did not change the Grin1 and Grin2A gene expression in these structures. In conclusion, NMDA receptor subunit modulation observed following cocaine abstinence with extinction training may represent a potential target in cocaine-seeking behavior.

摘要

不同的谷氨酸能系统中的神经元改变似乎对可卡因寻求行为的发展至关重要。可卡因暴露会引起啮齿动物 NMDA 受体亚单位表达的调节,这可能有助于可卡因引起的行为改变。本研究的目的是在可卡因戒断后(i)在丰富环境中,(ii)在隔离条件下,(iii)进行消退训练,或(iv)没有仪器任务的情况下,检查可卡因自我给药史大鼠脑结构中 NMDA 受体亚单位的组成,以及在大鼠脑结构中进行 10 天消退训练后评估 Grin1(编码 GluN1)和 Grin2A(编码 GluN2A)基因表达。在本研究中,我们仅观察到在进行消退训练的可卡因戒断后才发生变化,此时在先前自我给予可卡因的大鼠的前额皮质(PLC)和背侧海马(dHIP)的突触后密度部分而非整个匀浆中观察到 GluN2A 亚单位水平升高。同时,消退训练并未改变这些结构中 Grin1 和 Grin2A 基因的表达。总之,在进行消退训练的可卡因戒断后观察到的 NMDA 受体亚单位调节可能代表可卡因寻求行为的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b2e/8096759/adca32afa071/12640_2021_350_Fig1_HTML.jpg

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