Loscertales M, Rose S P, Daisley J N, Sandi C
Brain and Behaviour Research Group, The Open University, Milton Keynes, UK.
Eur J Neurosci. 1998 Jul;10(7):2238-43. doi: 10.1046/j.1460-9568.1998.00234.x.
We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.
我们研究了促智药吡拉西坦对一日龄雏鸡被动回避任务学习和记忆形成的影响。为了测试吡拉西坦可能的认知增强特性,我们使用了该任务的一个弱学习版本——雏鸡要记住避免啄食涂有稀释厌恶剂的珠子长达10小时。训练后(5、30或60分钟)而非训练前注射吡拉西坦(10或50毫克/千克,腹腔注射),当在24小时后对雏鸡进行测试时,会提高其对该任务的记忆再现。因为先前的研究表明被动回避任务的长期记忆依赖于脑皮质类固醇作用,并且因为吡拉西坦类化合物的功效也受皮质类固醇调节,所以我们测试了吡拉西坦的促进作用是否通过特定脑受体(盐皮质激素受体和糖皮质激素受体)依赖于皮质类固醇作用。首先,在注射吡拉西坦5分钟后发现血浆皮质酮水平升高。此外,在给予促智药之前脑内注射每种受体类型的拮抗剂(盐皮质激素受体拮抗剂RU28318和糖皮质激素受体拮抗剂RU38486;脑内注射)会抑制吡拉西坦对记忆巩固的促进作用。这些结果进一步支持了吡拉西坦通过一种神经作用对长期记忆形成所涉及机制的调节作用,在这个学习模型中,这种神经作用需要激活两种类型的细胞内皮质类固醇受体。