Ferger B, Stahl D, Kuschinsky K
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):545-51. doi: 10.1007/BF00169174.
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.
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。
