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可卡因反复给药后,其对大鼠脑电图功率谱的影响会发生显著改变:这些改变是否反映了敏感化现象?

Effects of cocaine on the EEG power spectrum of rats are significantly altered after its repeated administration: do they reflect sensitization phenomena?

作者信息

Ferger B, Stahl D, Kuschinsky K

机构信息

Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):545-51. doi: 10.1007/BF00169174.

Abstract

It was previously shown that a moderate dose of cocaine (10 mg/kg i.p.) produces a pattern in the EEG power spectrum which indicates a preferential activation of dopamine D1-like receptors, namely a decrease of power in most of the frequency bands. In contrast, a large dose of cocaine (30 mg/kg i.p.) produces a decrease of power in most of the frequency bands as well, but a selective increase in the alpha-1 band, characteristic for an additional activation of dopamine D2-like receptors. In the present experiments, it was studied in rats, if in the course of sensitization, a shift from D1-like to additional D2-like receptor activation will occur or not. For this study, the animals were treated 10 times with cocaine (either 10 or 20 mg/kg) and, after a drug free interval of 4 days, tested with the same dose administered previously. Acute administration of 10 mg/kg of cocaine increased the locomotor activity slightly and its effect tended to be enhanced after repeated administration. Twenty mg/kg cocaine increased the locomotor activity more than the 10 mg/kg dose and its effect was significantly enhanced after repeated treatment. In addition, it was shown that the dose of 10 mg/kg of cocaine which activates D1- but not D2-like receptors is sufficient to elicit conditioned place preference. Ten mg/kg of cocaine produced a decrease of power in most of the frequency bands and this effect was slightly more pronounced after repeated treatment. Twenty mg/kg of cocaine acutely also produced a decrease in power in most of the frequency bands, but did not decrease the power in the alpha-1 band, being just at the threshold of activating D2-like receptors as well. Repeated administration led to a significant increase in power in the alpha-1 band and a less pronounced one in the alpha-2 band. This observation demonstrates that sensitization to cocaine can be manifest in the EEG and that after a certain dosage, a shift from an activation of D1-like dopamine receptors to an additional activation of D2-like receptors becomes obvious.

摘要

先前的研究表明,中等剂量的可卡因(腹腔注射10毫克/千克)会在脑电图功率谱中产生一种模式,这表明多巴胺D1样受体被优先激活,即在大多数频段功率下降。相比之下,大剂量的可卡因(腹腔注射30毫克/千克)也会使大多数频段的功率下降,但α-1频段会选择性增加,这是多巴胺D2样受体额外激活的特征。在本实验中,研究了大鼠在致敏过程中是否会从D1样受体激活转变为额外的D2样受体激活。在这项研究中,给动物用可卡因(10或20毫克/千克)处理10次,在4天的无药间隔后,用先前给予的相同剂量进行测试。急性给予10毫克/千克可卡因会轻微增加运动活性,重复给药后其效果有增强的趋势。20毫克/千克可卡因比10毫克/千克剂量更能增加运动活性,重复处理后其效果显著增强。此外,已表明激活D1样而非D2样受体的10毫克/千克可卡因剂量足以引发条件性位置偏好。10毫克/千克可卡因使大多数频段的功率下降,重复处理后这种效果略为明显。20毫克/千克可卡因急性给药也会使大多数频段的功率下降,但不会使α-1频段的功率下降,其剂量也刚好处于激活D2样受体的阈值。重复给药导致α-1频段功率显著增加,α-2频段增加程度较小。这一观察结果表明,对可卡因的致敏可在脑电图中表现出来,并且在一定剂量后,从激活D1样多巴胺受体转变为额外激活D2样受体变得明显。

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