Wayner M J, Armstrong D L, Phelix C F
Division of Life Sciences, University of Texas at San Antonio 78249-0662, USA.
Peptides. 1996;17(7):1127-33. doi: 10.1016/s0196-9781(96)00179-9.
Angiotensin (ANG)-containing axons, terminals, and receptors have been found in the hippocampus. When angiotensin II (ANG II) is administered to the dentate gyrus, long-term potentiation (LTP) induction, in response to medial perforant path stimulation, is inhibited and it can be blocked by losartan, an ANG II AT1 receptor antagonist. ANG II has been shown to mediate impairment of the retention of an inhibitory shock avoidance response and to be involved in ethanol and diazepam inhibition of dentate gyrus LTP, all of which can be blocked by losartan. Nicotine acetylcholine receptors are found in the hippocampus and nicotine is involved in the enhancement of complex and important psychological functions that are mediated by the hippocampus; therefore, the possibility that nicotine prevents the ANG II inhibition of dentate granule cell LTP was examined. Nicotine pretreatment reduced ANG II inhibition of LTP induction in a dose-dependent manner. Mecamylamine blocked the nicotine antagonism of ANG II-induced LTP inhibition and normal LTP occurred, whereas hexamethonium was ineffective in blocking these central effects of nicotine. Nicotine by itself did not affect normal LTP under these conditions. Nicotinic blocking of the ANG II inhibition of a frequency dependent type of synaptic plasticity provides a function for central nicotinic receptors and a possible mechanism of action a) to explain the enhancement of learning and memory by nicotine, b) an explanation for tobacco smoking while drinking alcohol, and c) a possible basis for the excessive use of tobacco in depression and schizophrenia that supports a possible therapeutic use of nicotine in some mental disorders.
在海马体中已发现含有血管紧张素（ANG）的轴突、终末和受体。当将血管紧张素II（ANG II）注入齿状回时，对内侧穿通通路刺激的反应中，长时程增强（LTP）的诱导受到抑制，且可被ANG II AT1受体拮抗剂氯沙坦阻断。ANG II已被证明介导抑制性回避反应记忆的损害，并参与乙醇和地西泮对齿状回LTP的抑制作用，所有这些均可被氯沙坦阻断。海马体中存在烟碱型乙酰胆碱受体，且尼古丁参与由海马体介导的复杂且重要心理功能的增强；因此，研究了尼古丁是否能防止ANG II对齿状颗粒细胞LTP的抑制作用。尼古丁预处理以剂量依赖的方式降低了ANG II对LTP诱导的抑制作用。美加明阻断了尼古丁对ANG II诱导的LTP抑制的拮抗作用，正常LTP出现，而六甲铵在阻断尼古丁的这些中枢效应方面无效。在这些条件下，尼古丁本身不影响正常LTP。烟碱型受体对ANG II抑制频率依赖性突触可塑性的阻断为中枢烟碱型受体提供了一种功能以及一种可能的作用机制：a）解释尼古丁对学习和记忆的增强作用；b）解释饮酒时吸烟的现象；c）为抑郁症和精神分裂症中过度吸烟提供可能的基础，这支持了尼古丁在某些精神障碍中可能的治疗用途。
