Gonzalez L E, Andrews N, File S E
UMDS Division of Pharmacology, Guy's Hospital, London, UK.
Brain Res. 1996 Sep 2;732(1-2):145-53. doi: 10.1016/0006-8993(96)00517-3.
In order to investigate the role of the 5-HT1A receptors of the amygdala in modulating anxiety, rats were implanted with bilateral cannulae aimed at the basolateral nucleus of the amygdala complex and infused with either artificial cerebrospinal fluid (aCSF) or the selective 5-HT1A receptor agonist 8-OH-DPAT (50-200 ng) and tested in two animal models of anxiety. In the elevated plus-maze test, no significant effects were detected in this dose range. In contrast, 8-OH-DPAT caused an overall reduction in levels of social investigation, thus indicating anxiogenic actions in the social interaction test. At 50 ng, 8-OH-DPAT had a selective action on anxiety, while at 200 ng there was a concomitant reduction in locomotor activity and, in some animals, signs of the 5-HT1A syndrome. Evidence that the anxiogenic effect of 8-OH-DPAT (50 ng) was due to activation of 5-HT1A receptors came from the finding that (-)-tertatolol, a 5-HT1A receptor antagonist, reversed this effect at a dose (1.5 micrograms) which was silent when given alone. The benzodiazepine receptor agonist, midazolam (1 and 2 micrograms) was bilaterally administered into the basolateral nucleus of the amygdala and evoked clear-cut anxiolytic effects in the social interaction test. These data indicate that the agonist activation of post-synaptic 5-HT1A receptors in the basolateral nucleus of the amygdala may produce anxiogenic effects, while agonist activation of BDZ receptors in the same areas evokes anxiolytic effects. Our results from the social interaction test are similar to those previously reported from tests of anxiety using punished paradigms, but contrast with those found in the elevated plus-maze. Thus, it is concluded that either the two tests have different sensitivities to midazolam and 8-OH-DPAT or more intriguingly, the tests are evoking fundamentally different states of anxiety, with that evoked by the plus-maze being mediated via brain areas or receptors different from those studied here.
为了研究杏仁核5-羟色胺1A（5-HT1A）受体在调节焦虑中的作用，给大鼠双侧植入针对杏仁复合体基底外侧核的套管，并注入人工脑脊液（aCSF）或选择性5-HT1A受体激动剂8-羟基二丙胺基四氢萘（8-OH-DPAT，50 - 200纳克），然后在两种焦虑动物模型中进行测试。在高架十字迷宫试验中，在这个剂量范围内未检测到显著影响。相反，8-OH-DPAT导致社交探究水平总体下降，从而表明在社交互动试验中具有致焦虑作用。50纳克时，8-OH-DPAT对焦虑有选择性作用，而200纳克时，运动活动同时减少，在一些动物中出现5-HT1A综合征的迹象。8-OH-DPAT（50纳克）的致焦虑作用是由于5-HT1A受体激活的证据来自以下发现：5-HT1A受体拮抗剂（-）-特他洛尔在剂量为1.5微克时可逆转此效应，该剂量单独给药时无作用。将苯二氮䓬受体激动剂咪达唑仑（1和2微克）双侧注入杏仁核基底外侧核，并在社交互动试验中产生明显的抗焦虑作用。这些数据表明，杏仁核基底外侧核中突触后5-HT1A受体的激动剂激活可能产生致焦虑作用，而同一区域中苯二氮䓬（BDZ）受体的激动剂激活则产生抗焦虑作用。我们在社交互动试验中的结果与先前使用惩罚范式进行的焦虑试验报告的结果相似，但与高架十字迷宫试验中的结果相反。因此，可以得出结论，要么这两种试验对咪达唑仑和8-OH-DPAT的敏感性不同，要么更有趣的是，这两种试验引发的焦虑状态根本不同，高架十字迷宫试验引发的焦虑是通过与本文研究不同的脑区或受体介导的。
