Griebel G
CNS Research Department, Synthélabo Recherche, Bagneux, France.
Pol J Pharmacol. 1996 Mar-Apr;48(2):129-36.
To date, more than two thousand experiments have investigated the behavioral effect of 5-HT-interacting drugs in animal models of anxiety disorders. Most of them have focused on the involvement of drugs interacting with 5-HT1A, 5-HT2A/2C and 5-HT3 receptors. Although numerous results are in line with the classic 5-HT hypothesis of anxiety, suggesting that decreased anxiety is related to decreased activity in central 5-HT neurons and vice versa, paradoxical drug effects have often been found. To explain this variability, several authors point to a determining role of the experimental paradigms used. In fact, an overview of the behavioral data arising from the vast literature indicates that conditioned procedures as well as more ethological-based tests are equal in revealing anxiolytic-like effects of drugs targetting 5-HT1A, 5-HT2A or 5-HT2C receptor subtypes. Furthermore, results obtained in ethologically-based animal models of anxiety with drugs stimulating 5-HT transmission are most consistent with the classic 5-HT hypothesis of anxiety in that they showed an increase in animals' emotional reactivity. Finally, anxiolytic-like effects of 5-HT3 receptor antagonists are in great part revealed by models based on spontaneous behaviors. Taken together, these observations lead to the conclusion that different 5-HT mechanisms, mediated by different receptor subtypes, are involved in the genesis of anxiety.
迄今为止，已有两千多项实验研究了5-羟色胺（5-HT）相互作用药物在焦虑症动物模型中的行为效应。其中大多数研究聚焦于与5-HT1A、5-HT2A/2C和5-HT3受体相互作用的药物。尽管众多研究结果与经典的5-HT焦虑假说相符，即焦虑减轻与中枢5-HT神经元活动减少相关，反之亦然，但也常常发现一些矛盾的药物效应。为了解释这种变异性，一些作者指出所采用的实验范式起了决定性作用。事实上，对大量文献中的行为数据进行综述后发现，条件性实验程序以及更多基于行为学的测试在揭示针对5-HT1A、5-HT2A或5-HT2C受体亚型的药物的抗焦虑样效应方面效果相当。此外，在基于行为学的焦虑动物模型中，使用刺激5-HT传递的药物所获得的结果与经典的5-HT焦虑假说最为一致，因为这些结果显示动物的情绪反应性增加。最后，5-HT3受体拮抗剂的抗焦虑样效应在很大程度上是通过基于自发行为的模型揭示的。综上所述，这些观察结果得出结论，即由不同受体亚型介导的不同5-HT机制参与了焦虑的发生。
