Niehoff D L, Kuhar M J
J Neurosci. 1983 Oct;3(10):2091-7. doi: 10.1523/JNEUROSCI.03-10-02091.1983.
Behavioral, electroencephalographic, and evoked potential studies, as well as experiments utilizing the direct intracerebral injection of benzodiazepines (BZs), have implicated the amygdala, particularly its basolateral nuclear division, as an important locus of the therapeutic actions of these drugs. BZ receptor localization within the amygdala could further define which amygdaloid nuclei are important for BZ action and suggest neuroanatomical pathways especially sensitive to these drugs. Using a quantitative light microscopic autoradiographic technique, this study has localized type 1 and type 2 BZ receptors within the amygdaloid nuclear complex of the rat. BZ receptors were labeled with [3H]flunitrazepam, and type 1 BZ receptor binding was preferentially displaced by CL218,872 in 8-micron coronal sections of rat brain. Autoradiograms were generated by the apposition of emulsion-coated coverslips and quantified by standardized procedures. Ten amygdaloid nuclei were examined at nine levels over the rostrocaudal extent of the amygdala. Total BZ receptor density was highest in the basolateral nuclear complex, and the majority of these receptors were of the type 2 subclass. Type 1 receptors were concentrated in the anterior aspects of the amygdala, particularly the anterior cortical nucleus. These results are consistent with an important role for the basolateral amygdala in anxiogenesis and seizure induction. Furthermore, a larger circuit which includes the amygdala, ventromedial hypothalamus, mammillary body, anterior thalamus, and frontal cortex could be involved in the anxiolytic actions of the BZ drugs.
行为学、脑电图及诱发电位研究,以及利用苯二氮䓬类药物(BZs)直接脑内注射的实验表明,杏仁核,尤其是其基底外侧核团,是这些药物治疗作用的重要位点。杏仁核内BZ受体的定位可以进一步明确哪些杏仁核核团对BZ作用至关重要,并提示对这些药物特别敏感的神经解剖学通路。本研究采用定量光学显微镜放射自显影技术,在大鼠杏仁核复合体中定位了1型和2型BZ受体。用[3H]氟硝西泮标记BZ受体,在大鼠脑8微米冠状切片中,CL218,872优先取代1型BZ受体结合。通过将涂有乳剂的盖玻片并置产生放射自显影片,并通过标准化程序进行定量。在杏仁核的前后范围内,在九个层面检查了十个杏仁核核团。总BZ受体密度在基底外侧核复合体中最高,且这些受体中的大多数属于2型亚类。1型受体集中在杏仁核的前部,尤其是前皮质核。这些结果与基底外侧杏仁核在焦虑症发生和癫痫诱导中的重要作用一致。此外,一个包括杏仁核、腹内侧下丘脑、乳头体、前丘脑和额叶皮质的更大回路可能参与了BZ药物的抗焦虑作用。