Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
J Psychopharmacol. 1996 Jan;10(3):206-13. doi: 10.1177/026988119601000305.
The effects of four BZ receptor ligands in an operant test were compared with a rotarod test. In the operant test, rats were trained to pull a chain on a schedule that regulates the probability of delivery of food pellets to maintain a steady chain-pulling rate across a 1 h test session. For the rotarod test, mice were trained to remain on a rotarod for 2 min. Diazepam (0.1-3.0 mg/kg, i.p.), FG 8205 (0.1-3.0 mg/kg, i.p.), quazepam (3.0-60.0 mg/kg, i.p.) and zolpidem (0.3-10.0 mg/kg, i.p.) each produced dose-related impairments of performance in both the chain- pulling test and the mouse rotarod test. Furthermore, the impairment in performance induced by FG 8205 (10.0 mg/kg, p.o.) was dose-dependently reversed by the BZ receptor antagonist, flumazenil (1.0-10.0 mg/kg, i.p.), indicating that the chain-pulling deficit was mediated via BZ receptor activation. Diazepam, FG 8205 and quazepam all had comparable potencies in both the rotarod assay and the chain-pulling test. However, zolpidem suppressed the chain-pulling rates at a dose 30-fold lower than that required to induce a significant deficit in the rotarod performance. As zolpidem is a preferentially sedative compound, this pattern of results is consistent with the hypothesis that the chain-pulling test is sensitive to sedation induced by BZ receptor agonists.
四种 BZ 受体配体在操作性测试中的影响与转棒测试进行了比较。在操作性测试中，大鼠接受训练，按调节食物颗粒传递概率的时间表拉动链条，以在 1 小时测试过程中保持稳定的链条拉动率。对于转棒测试，训练小鼠在转棒上停留 2 分钟。地西泮（0.1-3.0mg/kg，ip）、FG 8205（0.1-3.0mg/kg，ip）、夸西泮（3.0-60.0mg/kg，ip）和唑吡坦（0.3-10.0mg/kg，ip）都在链拉测试和小鼠转棒测试中产生了剂量相关的性能障碍。此外，FG 8205（10.0mg/kg，po）引起的性能障碍被 BZ 受体拮抗剂氟马西尼（1.0-10.0mg/kg，ip）剂量依赖性地逆转，表明链拉缺陷是通过 BZ 受体激活介导的。地西泮、FG 8205 和夸西泮在转棒试验和链拉试验中的效力相当。然而，唑吡坦在抑制链拉率的剂量比在转棒性能中引起显著缺陷所需的剂量低 30 倍。由于唑吡坦是一种优先镇静的化合物，这种结果模式与链拉试验对 BZ 受体激动剂诱导镇静敏感的假设一致。
