Schulte D, Callado L F, Davidson C, Phillips P E, Roewer N, Schulte am Esch J, Stamford J A
Department of Anaesthesiology, University Hospital Eppendorf, Hamburg, Germany.
Br J Anaesth. 2000 Feb;84(2):250-3. doi: 10.1093/oxfordjournals.bja.a013413.
Although propofol (2,6-di-isopropylphenol) is a popular i.v. general anaesthetic, it has been suggested to have abuse potential. As many drugs of abuse act preferentially via release of dopamine in the limbic system, we investigated the action of propofol on stimulated dopamine release in the rat nucleus accumbens. Nucleus accumbens slices were superfused (1.6 ml min-1) with artificial cerebrospinal fluid at 32 degrees C. Dopamine release was evoked by electrical stimulation (10 pulses, 0.1 ms, 10 mA, 10 Hz, every 10 min) and monitored by fast cyclic voltammetry. Propofol 100 mumol litre-1 reduced stimulated dopamine release over the 2 h after administration, relative to intralipid controls, to mean 30 (SEM 2)% (P < 0.01). The dopamine D2 receptor antagonist metoclopramide 0.3 mumol litre-1 increased dopamine release but did not block the effect of propofol (38 (3)%). The selective GABAA antagonist bicuculline 24 mumol litre-1 also failed to antagonize the action of propofol (45 (3)%). The NMDA receptor antagonist dextromethorphan 10 mumol litre-1 decreased dopamine release to 57 (6)% (P < 0.01) but failed to block the inhibitory effect of propofol (46 (6)%). Although propofol has been reported to bind to D2, GABAA and NMDA receptors, failure of metoclopramide and bicuculline to block its effects suggests that an agonist action at D2 or GABAA receptors does not mediate the effects of propofol on dopamine release in the rat nucleus accumbens. The lack of effect of dextromethorphan makes an NMDA receptor antagonist action unlikely.
尽管丙泊酚（2,6 - 二异丙基苯酚）是一种常用的静脉全身麻醉药，但有人认为它具有被滥用的可能性。由于许多滥用药物主要通过边缘系统中多巴胺的释放起作用，我们研究了丙泊酚对大鼠伏隔核中刺激诱导的多巴胺释放的作用。将伏隔核切片在32℃下用人工脑脊液以1.6 ml·min⁻¹的速度进行灌流。通过电刺激（10个脉冲，0.1 ms，10 mA，10 Hz，每10分钟一次）诱发多巴胺释放，并通过快速循环伏安法进行监测。相对于脂质乳剂对照组，100 μmol·L⁻¹的丙泊酚在给药后2小时内使刺激诱导的多巴胺释放减少至平均30（标准误2）%（P < 0.01）。0.3 μmol·L⁻¹的多巴胺D2受体拮抗剂甲氧氯普胺增加了多巴胺释放，但并未阻断丙泊酚的作用（38（3）%）。24 μmol·L⁻¹的选择性GABAA拮抗剂荷包牡丹碱也未能拮抗丙泊酚的作用（45（3）%）。10 μmol·L⁻¹的NMDA受体拮抗剂右美沙芬使多巴胺释放减少至57（6）%（P < 0.01），但未能阻断丙泊酚的抑制作用（46（6）%）。尽管有报道称丙泊酚可与D2、GABAA和NMDA受体结合，但甲氧氯普胺和荷包牡丹碱未能阻断其作用，这表明其对D2或GABAA受体的激动作用并不能介导丙泊酚对大鼠伏隔核中多巴胺释放的影响。右美沙芬无效表明其不太可能通过NMDA受体拮抗剂作用发挥影响。
