File S E, Kenny P J, Cheeta S
Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, SE1 IUL, London, UK.
Pharmacol Biochem Behav. 2000 May;66(1):65-72. doi: 10.1016/s0091-3057(00)00198-2.
A review of the literature suggests that the dorsal hippocampal serotonergic system, and, in particular, the postsynaptic 5-HT(1A) receptor, mediates an anxiogenic response, whereas endogenous dorsal hippocampal cholinergic tone mediates an anxiolytic response. Accordingly, it has been shown that direct dorsal hippocampal administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, the nicotinic receptor antagonist, mecamylamine, and the M(1) muscarinic receptor antagonist, pirenzepine, all have anxiogenic effects in rats tested in the social interaction test. It is therefore surprising that nicotine also has an anxiogenic effect in this test following dorsal hippocampal administration. However, the anxiogenic effects of mecamylamine and nicotine in the dorsal hippocampus are blocked by coadministration of the 5-HT(1A) receptor antagonist, WAY 100635, suggesting that both of these compounds act by enhancing hippocampal serotonergic transmission, thereby stimulating postsynaptic 5-HT(1A) receptors. This conclusion is supported by the observation that both nicotine and mecamylamine stimulate basal [3H]-5-HT release from dorsal hippocampal slices. A possible mechanism by which nicotinic receptor ligands modulate hippocampal 5-HT release is discussed, and it is proposed that the dorsal hippocampal serotonergic and cholinergic systems are tightly coupled and function antagonistically in the modulation of anxiety, as measured in the social interaction test. These systems are relatively unimportant in controlling behaviour on trial 1 in the plus-maze. On trial 2 in the elevated plus-maze, a model of specific phobia, the endogenous cholinergic system, nicotine, and the M(1) receptor agonist, McN-A-343, all mediate an anxiolytic effect, whereas stimulation of 5-HT(1A) receptors mediates an anxiogenic effect. It is proposed that the hippocampus may predominantly control the avoidance components of phobic anxiety, with other regions, such as the dorsomedial hypothalamus, controlling the escape components.
文献综述表明，背侧海马体5-羟色胺能系统，尤其是突触后5-HT(1A)受体，介导焦虑反应，而内源性背侧海马体胆碱能张力介导抗焦虑反应。因此，研究表明，在社交互动试验中，直接向背侧海马体注射5-HT(1A)受体激动剂8-OH-DPAT、烟碱受体拮抗剂美加明以及M(1)毒蕈碱受体拮抗剂哌仑西平，对大鼠均有焦虑诱导作用。因此，令人惊讶的是，在背侧海马体给药后，尼古丁在该试验中也具有焦虑诱导作用。然而，美加明和尼古丁在背侧海马体中的焦虑诱导作用被同时给予的5-HT(1A)受体拮抗剂WAY 100635所阻断，这表明这两种化合物均通过增强海马体5-羟色胺能传递，从而刺激突触后5-HT(1A)受体发挥作用。这一结论得到了以下观察结果的支持：尼古丁和美加明均能刺激背侧海马体切片中基础[3H]-5-羟色胺的释放。本文讨论了烟碱受体配体调节海马体5-羟色胺释放的可能机制，并提出背侧海马体5-羟色胺能和胆碱能系统紧密耦合，在社交互动试验中测量的焦虑调节中发挥拮抗作用。这些系统在控制加迷宫试验第1次试验中的行为方面相对不重要。在高架加迷宫试验的第2次试验中，作为特定恐惧症模型，内源性胆碱能系统、尼古丁和M(1)受体激动剂McN-A-343均介导抗焦虑作用，而刺激5-HT(1A)受体则介导焦虑诱导作用。有人提出，海马体可能主要控制恐惧焦虑的回避成分，而其他区域，如下丘脑背内侧，控制逃避成分。
