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加兰他敏有助于健康幼兔获得痕迹条件性眨眼反应。

Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits.

作者信息

Simon Barbara B, Knuckley Bryan, Powell Donald A

机构信息

Shirley L. Buchanan Neuroscience Laboratory, WJB Dorn VA Medical Center, Columbia, South Carolina 29209, USA.

出版信息

Learn Mem. 2004 Jan-Feb;11(1):116-22. doi: 10.1101/lm.66204.

Abstract

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of an eyeblink (EB) classical conditioning task in healthy, young animals. We trained 24 rabbits (n = 8/group) in a 1000-msec trace Pavlovian EB conditioning paradigm in which a tone conditioned stimulus (CS) was presented for 500 msec, followed by a 500-msec trace period in which no stimuli were presented. A 100-msec corneal airpuff was the unconditioned stimulus (US). Acquisition sessions, consisting of 100 trials each, occurred daily for 10 consecutive days, followed by 3 d of extinction training. Animals were treated with one of three doses of GAL (0.0-3.0 mg/kg) prior to each session. Animals that received 3.0 mg/kg GAL showed significantly more EB conditioned responses (CRs) in fewer training trials than animals receiving either 1.5 mg/kg GAL or vehicle injections. GAL had no effect on CR performance during extinction. Pseudoconditioning control experiments, consisting of 200 explicitly unpaired tone-puff presentations indicated that GAL did not increase reactivity to the CS or US. These findings indicate that GAL may improve acquisition of moderately difficult associative learning tasks in healthy young organisms.

摘要

先前的研究表明,能提高大脑乙酰胆碱浓度的药物可增强衰老及脑损伤生物体的认知能力。本研究评估了加兰他敏(GAL),一种烟碱型胆碱能受体的变构调节剂及弱乙酰胆碱酯酶抑制剂,是否能改善健康幼龄动物眨眼(EB)经典条件反射任务的获得和保持。我们在一个1000毫秒的痕迹巴甫洛夫式EB条件反射范式中训练了24只兔子(每组n = 8只),其中一个音调条件刺激(CS)呈现500毫秒,随后是500毫秒的痕迹期,在此期间不呈现任何刺激。一个100毫秒的角膜吹气是无条件刺激(US)。每天进行一次由100次试验组成的获得训练,连续进行10天,随后进行3天的消退训练。在每次训练前,动物接受三种剂量之一的GAL(0.0 - 3.0毫克/千克)治疗。接受3.0毫克/千克GAL治疗的动物在比接受1.5毫克/千克GAL或注射赋形剂的动物更少的训练试验中表现出明显更多的EB条件反应(CRs)。GAL在消退过程中对CR表现没有影响。由200次明确不配对的音调 - 吹气呈现组成的伪条件控制实验表明,GAL不会增加对CS或US的反应性。这些发现表明,GAL可能改善健康幼龄生物体中中等难度联想学习任务的获得。

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