el-Zahaby H M, Ghoneim M M, Johnson G M, Gormezano I
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242.
Anesthesiology. 1994 Jul;81(1):229-37. doi: 10.1097/00000542-199407000-00029.
Evidence concerning the concentrations of volatile anesthetics that prevent learning and recall is limited. Epinephrine is believed to enable learning during anesthesia. We investigated the effects of isoflurane and its interaction with epinephrine on learning and subsequent retention of the rabbit's classically conditioned nictitating membrane response.
In experiment 1, a tone (conditioned stimulus, CS) preceded paraorbital shock (unconditioned stimulus, US) during 60-min daily sessions of 60 presentations of these paired stimuli for 6 days of acquisition training under 0, 0.4%, or 0.8% isoflurane (n = 8, 13, and 9, respectively). Responses were recorded as conditioned responses (CRs) if they occurred during the CS and before the onset of the US. After 1 day of rest, the animals were given 3 days of extinction consisting of 60 presentations of CS-alone and without isoflurane to assess the retention of CRs from acquisition training. In experiment 2, epinephrine in a dose of 0, 0.01, or 0.1 mg/kg was injected subcutaneously in rabbits receiving 0.4% isoflurane. Two types of epinephrine were used, a sustained release form and epinephrine hydrochloride. Acquisition and retention were tested in the same way as in experiment 1. No isoflurane or epinephrine was used during retention testing.
Learning was significantly suppressed during 0.4% isoflurane (approximately equal to 0.2 MAC) treatment and eliminated during 0.8% (approximately equal to 0.4 MAC). Information learned during administration of 0.4% isoflurane was not retained (P < 0.05). Although the low doses of epinephrine improved learning during the last day of the acquisition phase (P < 0.05), there were no differences between the treatment groups on any of the remaining acquisition or extinction days.
There was no learning during treatment with 0.8% concentration. Even a 0.4% concentration, which allowed some learning, abolished CRs in extinction, perhaps because of state-dependent retrieval. Epinephrine did not alter substantially the rates of CR acquisition or resistance to extinction.
关于预防学习和记忆的挥发性麻醉剂浓度的证据有限。肾上腺素被认为能使动物在麻醉期间进行学习。我们研究了异氟烷及其与肾上腺素的相互作用对家兔经典条件性瞬膜反应的学习和后续记忆的影响。
在实验1中，在每天60分钟的训练时段内，在6天的习得训练中，音调（条件刺激，CS）先于眶周电击（非条件刺激，US）出现，这些配对刺激共呈现60次，分别在0%、0.4%或0.8%异氟烷浓度下进行（每组分别为8只、13只和9只）。如果反应发生在条件刺激期间且在非条件刺激开始之前，则记录为条件反应（CRs）。休息1天后，给予动物3天的消退训练，即单独呈现条件刺激且无异氟烷，以评估习得训练中条件反应的记忆情况。在实验2中，给接受0.4%异氟烷的家兔皮下注射剂量为0、0.01或0.1mg/kg的肾上腺素。使用了两种类型的肾上腺素，一种是缓释型，另一种是盐酸肾上腺素。习得和记忆测试方法与实验1相同。在记忆测试期间不使用异氟烷或肾上腺素。
在0.4%异氟烷（约等于0.2MAC）处理期间学习明显受到抑制，在0.8%（约等于0.4MAC）时学习被消除。在0.4%异氟烷给药期间学到的信息未被保留（P<0.05）。尽管低剂量肾上腺素在习得阶段的最后一天改善了学习（P<0.05），但在其余习得或消退天数中，各治疗组之间没有差异。
在8%浓度处理期间没有学习发生。即使是允许一定程度学习的4%浓度，也会在消退时消除条件反应，这可能是由于状态依赖的提取。肾上腺素并没有显著改变条件反应的习得率或对消退的抵抗力。
