Raffalli-Sebille M J, Chapouthier G, Venault P, Dodd R H
Laboratoire de Génétique, Neurogénétique et Comportement U.R.A. 1294 C.N.R.S., U.E.R. Biomedicale, Université Paris V, France.
Pharmacol Biochem Behav. 1990 Feb;35(2):281-4. doi: 10.1016/0091-3057(90)90156-c.
In contrast to diazepam, a benzodiazepine receptor (BZ-R) ligand, which impairs memory processing, methyl beta-carboline-3-carboxylate (beta-CCM), another BZ-R ligand, administered before a training session, enhances performance in a retention test. This action, however, has only been demonstrated in single trial or single session learning protocols. The present report extends these results to a multiple-trial learning procedure in mice (brightness discrimination in a T-maze with negative reinforcement). The animals were trained for sessions of ten trials per day for six consecutive days. In a first experiment, the sessions during the first three days took place after administration of beta-CCM (0.3 mg/kg), diazepam (2.5 mg/kg) or saline. In a second experiment, especially designed to study the effects of beta-CCM, during the first three days animals received beta-CCM (0.3 mg/kg), Ro 15-1788 (15 mg/kg), beta-CCM + Ro 15-1788, vehicles of these drugs or saline. In the first experiment, performance was improved by beta-CCM and impaired by diazepam in the first three sessions as well as in the final three. In the second experiment, beta-CCM alone, as well as Ro 15-1788 improved performance, and the simultaneous administration of the two drugs suppressed these effects. These results suggest that the performance enhancing effects of beta-CCM observed in single trial learning protocols, during the retention test, can already be observed during drug treatment. They confirm that beta-CCM has an action on acquisition (learning). As the effects of beta-CCM are suppressed by the simultaneous administration of Ro 15-1788, our results could suggest a role for benzodiazepine receptors in learning. This question is discussed.
与地西泮（一种会损害记忆处理的苯二氮䓬受体（BZ-R）配体）不同，另一种BZ-R配体β-咔啉-3-羧酸甲酯（β-CCM）在训练前给药，可提高记忆测试中的表现。然而，这种作用仅在单次试验或单节学习方案中得到证实。本报告将这些结果扩展至小鼠的多次试验学习程序（在带有负强化的T迷宫中进行亮度辨别）。动物连续六天每天接受十次试验的训练。在第一个实验中，前三天的试验在给予β-CCM（0.3毫克/千克）、地西泮（2.5毫克/千克）或生理盐水后进行。在第二个实验中，特别设计用于研究β-CCM的作用，在前三天动物接受β-CCM（0.3毫克/千克）、Ro 15-1788（15毫克/千克）、β-CCM + Ro 15-1788、这些药物的载体或生理盐水。在第一个实验中，β-CCM在前三个试验节段以及最后三个试验节段均提高了表现，而地西泮则损害了表现。在第二个实验中，单独使用β-CCM以及Ro 15-1788均提高了表现，而两种药物同时给药则抑制了这些作用。这些结果表明，在单次试验学习方案中观察到的β-CCM在记忆测试期间的表现增强作用，在药物治疗期间即可观察到。它们证实β-CCM对习得（学习）有作用。由于同时给予Ro 15-1788可抑制β-CCM的作用，我们的结果可能提示苯二氮䓬受体在学习中起作用。对此问题进行了讨论。
