Idemudia S O, Mathis D A, Lal H
Department of Pharmacology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Neuropharmacology. 1987 Dec;26(12):1739-43. doi: 10.1016/0028-3908(87)90126-2.
The role of the GABA system in producing a pentylenetetrazol-like interoceptive discriminative stimulus during withdrawal from diazepam was investigated in rats by determining the sensitivity of this system to GABAergic drugs before and after chronic treatment with diazepam. Food-restricted rats were trained to obtain a reward of food by responding on one lever following an injection of pentylenetetrazol (PTZ; 20 mg/kg) and the other lever following an injection of saline (1 ml/kg). After rats had acquired this discrimination, the effectiveness of Ro 15-1788, bicuculline and yohimbine to substitute for pentylenetetrazol was determined. Prior to chronic treatment with diazepam, rats selected the appropriate lever for saline after Ro 15-1788 and the appropriate lever for pentylenetetrazol after bicuculline (0.04-2.5 mg/kg) or yohimbine (0.16-5.0 mg/kg). Although the selection of the appropriate lever for pentylenetetrazol was dose-dependent, full substitution for pentylenetetrazol was not obtained with either drug as larger doses of bicuculline produced convulsions while the rats began to select the appropriate lever for saline after larger doses of yohimbine (bell-shaped curve). Diazepam blocked the pentylenetetrazol-like interoceptive discriminative stimulus for bicuculline. The rats were then injected with diazepam (80 mg/kg/8 hr) for 24 days. Upon termination of the administration of diazepam, the animals were tested for lever-selection following the administration of saline, Ro 15-1788 (10 mg/kg), bicuculline (0.32, 0.64 and 1.25 mg/kg) or yohimbine (0.16, 0.64 and 2.5 mg/kg). After saline, 33% of the rats selected the appropriate lever for pentylenetetrazol whereas selection of this lever was enhanced after Ro 15-1788, bicuculline or yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)
通过测定慢性地西泮治疗前后GABA系统对GABA能药物的敏感性，研究了大鼠在从地西泮戒断过程中GABA系统在产生戊四氮样内感受性辨别刺激中的作用。对食物限制的大鼠进行训练，使其在注射戊四氮（PTZ；20mg/kg）后按压一个杠杆以获得食物奖励，在注射生理盐水（1ml/kg）后按压另一个杠杆以获得食物奖励。大鼠获得这种辨别能力后，测定Ro 15-1788、荷包牡丹碱和育亨宾替代戊四氮的有效性。在地西泮慢性治疗前，大鼠在注射Ro 15-1788后选择与生理盐水对应的杠杆，在注射荷包牡丹碱（0.04-2.5mg/kg）或育亨宾（0.16-5.0mg/kg）后选择与戊四氮对应的杠杆。虽然选择与戊四氮对应的杠杆呈剂量依赖性，但两种药物均未完全替代戊四氮，因为较大剂量的荷包牡丹碱会引起惊厥，而大鼠在注射较大剂量的育亨宾后开始选择与生理盐水对应的杠杆（钟形曲线）。地西泮阻断了荷包牡丹碱的戊四氮样内感受性辨别刺激。然后给大鼠注射地西泮（80mg/kg/8小时），持续24天。在地西泮给药结束后，给动物注射生理盐水、Ro 15-1788（10mg/kg）、荷包牡丹碱（0.32、0.64和1.25mg/kg）或育亨宾（0.16、0.64和2.5mg/kg）后进行杠杆选择测试。注射生理盐水后，33%的大鼠选择与戊四氮对应的杠杆，而在注射Ro 15-1788、荷包牡丹碱或育亨宾后，选择该杠杆的比例增加。（摘要截断于250字）
