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大鼠对反复给予可卡因的适应性

Adaptation to repeated cocaine administration in rats.

作者信息

Binienda Zbigniew K, Pereira Frederico, Alper Kenneth, Slikker William, Ali Syed F

机构信息

Division of Neurotoxicology, NCTR/FDA, Jefferson, Arkansas 72029, USA.

出版信息

Ann N Y Acad Sci. 2002 Jun;965:172-9. doi: 10.1111/j.1749-6632.2002.tb04159.x.

Abstract

Quantitative electroencephalogram (EEG) studies in cocaine-dependent human patients show deficits in slow-wave brain activity, reflected in diminished EEG power in the delta and theta frequency bands. In the present study, electrophysiological measures were monitored in 10 nonanesthetized, adult male Sprague-Dawley rats via bipolar, epidural electrodes implanted over the somatosensory cortex. Control electrocorticograms (ECoG) were recorded twice within a two-week interval to establish a baseline. Rats were subsequently injected daily with cocaine HCl at 15 mg/kg, i.p., for two weeks. The ECoG was recorded during a 1-h session one day after the last injection. Total concentrations of dopamine (DA) and its metabolites were assayed in caudate nucleus (CN) and frontal cortex (FC) using HPLC/EC. Compared with controls, marked increases in DA concentrations were observed in both regions. The DA turnover decreased significantly. The power spectra, obtained by use of a fast Fourier transformation, revealed a significant decrease in slow-wave delta frequency bands following repeated exposure to cocaine. These data are consistent with reported findings in humans that repeated exposures to cocaine result in a decrease in slow-wave brain activity. Further studies are necessary to establish whether regional alterations in blood flow and metabolic activity may underlie such observations.

摘要

对可卡因成瘾的人类患者进行的定量脑电图(EEG)研究显示,慢波脑活动存在缺陷,表现为δ和θ频段的脑电图功率降低。在本研究中,通过植入体感皮层上方的双极硬膜外电极,对10只未麻醉的成年雄性Sprague-Dawley大鼠进行电生理测量。在两周的间隔内记录两次对照脑电图(ECoG)以建立基线。随后,大鼠每天腹腔注射15 mg/kg的盐酸可卡因,持续两周。在最后一次注射后一天的1小时内记录ECoG。使用高效液相色谱/电化学检测法(HPLC/EC)测定尾状核(CN)和额叶皮层(FC)中多巴胺(DA)及其代谢物的总浓度。与对照组相比,两个区域的DA浓度均显著增加。DA周转率显著降低。通过快速傅里叶变换获得的功率谱显示,反复接触可卡因后,慢波δ频段显著降低。这些数据与在人类中报道的结果一致,即反复接触可卡因会导致慢波脑活动减少。有必要进一步研究以确定血流和代谢活动的区域改变是否可能是这些观察结果的基础。

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