Kulig B M
Pharmacol Biochem Behav. 1986 Jun;24(6):1805-7. doi: 10.1016/0091-3057(86)90526-5.
The effects of phenobarbital on coordinated locomotion were measured in rats trained to criterion to avoid electric shock by running treadmill fashion along a motor driven belt. Two phenobarbital groups (35 and 50 mg/kg) and saline controls were injected for 29 consecutive days. Testing was carried out on Drug Days 1, 15, and 29. On Drug Day 1, disturbances in gait and balance were reflected by an increased time off belt for the phenobarbital groups. In addition, both groups demonstrated a significant improvement in performance over the three 2-min trial test sessions. Deficits were further reduced on Drug Day 15, and by Drug Day 29, the performance of rats treated with 35 mg/kg was equivalent to control values while that of the 50 mg/kg group had improved by more than 90%. There was no corresponding change in plasma levels of phenobarbital during subacute dosing. After a one month drug withdrawal period, treatment with phenobarbital again produced coordination deficits which were equivalent to those seen on Drug Day 1. These data demonstrate that an attenuation of the effects of phenobarbital on coordination can begin within minutes of the initial test session and is most likely due to behavioral processes (i.e., acute functional tolerance). In addition, results suggest that further drug exposure may play a role in the carry-over of functional tolerance from one drug test session to the next.
通过训练大鼠以跑步机模式沿着电动皮带奔跑以达到避免电击的标准，来测量苯巴比妥对协调运动的影响。连续29天给两个苯巴比妥组（35和50毫克/千克）及生理盐水对照组注射药物。在给药第1天、第15天和第29天进行测试。在给药第1天，苯巴比妥组离开皮带的时间增加，反映出步态和平衡受到干扰。此外，两组在三个2分钟的试验测试时段内的表现均有显著改善。在给药第15天，缺陷进一步减少，到给药第29天，接受35毫克/千克治疗的大鼠的表现与对照组相当，而50毫克/千克组的表现提高了90%以上。在亚急性给药期间，苯巴比妥的血浆水平没有相应变化。经过一个月的停药期后，再次使用苯巴比妥治疗会再次产生与给药第1天所见相当的协调缺陷。这些数据表明，苯巴比妥对协调的影响减弱可能在初始测试时段的几分钟内就开始了，并且很可能是由于行为过程（即急性功能性耐受）。此外，结果表明，进一步接触药物可能在功能性耐受从一个药物测试时段延续到下一个时段中起作用。
