Young S L, Bohenek D L, Fanselow M S
Department of Psychology, University of California, Los Angeles 90024, USA.
Neurobiol Learn Mem. 1995 Mar;63(2):174-80. doi: 10.1006/nlme.1995.1018.
Cholinergic antagonism impacts selected learning tasks. To understand where scopolamine exerts its action, learning tasks differentially sensitive to hippocampus and amygdala lesions were used. Hippocampal lesions prevent context fear conditioning without effect on tone conditioning. These lesions also produce a time-dependent retrograde deficit in context conditioning. The amygdala is necessary for both tone and context conditioning. To examine the possibility that cholinergic antagonism mimics hippocampal damage or amygdala damage, rats were given scopolamine (1 mg/kg) either before or after fear conditioning. In the fear conditioning procedure, rats received tone-footshock or context-footshock pairings. Evidence of conditioning to the tone and the context was provided by observation of freezing. When given prior to training, scopolamine blocked fear conditioning to the tone in a dose-dependent fashion but had no effect on context conditioning. The impairment of tone conditioning did not occur with methylscopolamine, indicating the central action of the drug. Rats given scopolamine immediately following fear conditioning, tested later in a drug-free state, froze more to the tone than rats given a control injection. The effect of scopolamine on freezing to the context was not reliable. The present results suggest that scopolamine's impact on fear conditioning is mediated by some mechanism other than impaired hippocampal or amygdala functioning.
胆碱能拮抗作用会影响特定的学习任务。为了了解东莨菪碱的作用位点，研究人员使用了对海马体和杏仁核损伤敏感度不同的学习任务。海马体损伤会阻碍情境恐惧条件反射，而对音调条件反射没有影响。这些损伤还会在情境条件反射中产生时间依赖性的逆行缺陷。杏仁核对音调条件反射和情境条件反射都是必需的。为了检验胆碱能拮抗作用是否模拟了海马体损伤或杏仁核损伤，在恐惧条件反射之前或之后给大鼠注射东莨菪碱（1毫克/千克）。在恐惧条件反射过程中，大鼠接受音调-电击或情境-电击配对。通过观察僵住行为来提供对音调和情境进行条件反射的证据。在训练前给予东莨菪碱时，它以剂量依赖的方式阻断了对音调的恐惧条件反射，但对情境条件反射没有影响。甲基东莨菪碱不会导致音调条件反射受损，这表明该药物的中枢作用。在恐惧条件反射后立即给予东莨菪碱的大鼠，在之后无药物状态下进行测试时，与给予对照注射的大鼠相比，对音调的僵住反应更多。东莨菪碱对情境僵住反应的影响并不稳定。目前的结果表明，东莨菪碱对恐惧条件反射的影响是由海马体或杏仁核功能受损以外的某种机制介导的。
