Stahl D, Ferger B, Kuschinsky K
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):335-40. doi: 10.1007/pl00005059.
After repeated administration of cocaine or d-amphetamine, a sensitization to their behavioural effects is frequently observed instead of a tolerance. In a previous study, it was shown that a moderate dose of d-amphetamine produced a pattern of EEG power spectrum which indicated a selective activation of D1-like dopamine receptors, whereas a larger dose induced a selective increase of power in the alpha-1 frequency band and, to a lesser degree, in the alpha-2 band, suggesting an additional activation of D2-like receptors. Furthermore, it was recently found that under a certain dosage and schedule, cocaine could produce a shift from a D1-characteristic to a D2-like EEG pattern. It was now studied, if the same is true for d-amphetamine. This drug was administered on 4 subsequent days (0.6 mg/kg i.p.); after an interval of 3 days, the same dose was administered. After repeated, but not a single administration, increases in the power of the alpha-1 and alpha-2 frequency bands were observed, suggesting a shift from activation of D1-like to additional activation of D2-like receptors. This shift was accompanied by a slight enhancement in stereotyped behaviour (sniffing). After a lower dose (0.2 mg/kg), no EEG effect could be observed, neither after a single nor after repeated administration.
反复给予可卡因或右旋苯丙胺后，常观察到对其行为效应的敏化而非耐受。在先前的一项研究中，结果表明中等剂量的右旋苯丙胺会产生一种脑电图功率谱模式，这表明D1样多巴胺受体被选择性激活，而较大剂量则会导致α-1频段功率选择性增加，α-2频段功率也有较小程度增加，提示D2样受体被额外激活。此外，最近发现，在一定剂量和给药方案下，可卡因可使脑电图模式从D1特征性转变为D2样模式。现在研究右旋苯丙胺是否也如此。该药物在随后4天内每天腹腔注射0.6mg/kg；间隔3天后，给予相同剂量。反复给药而非单次给药后，观察到α-1和α-2频段功率增加，提示从D1样受体激活转变为D2样受体额外激活。这种转变伴随着刻板行为（嗅探）略有增强。给予较低剂量（0.2mg/kg）后，无论是单次给药还是反复给药，均未观察到脑电图效应。
