Yamada K, Hayashi T, Hasegawa T, Ishihara S, Kameyama T, Morimasa T, Kaneyuki T, Shohmori T, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):53-8. doi: 10.1254/jjp.66.53.
We investigated the effects of the long-term administration of Kamikihito (KKT) on the specific binding of [3H]muscimol and [3H]flunitrazepam in the brains of young and aged rats using in vitro quantitative autoradiography. Specific [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding did not change in any of the brain regions. Scatchard analysis revealed that the maximal number of [3H]muscimol binding sites in the cortex and thalamus was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. Long-term administration of KKT in young rats had no effect on either [3H]muscimol or [3H]flunitrazepam binding. In contrast, the same treatment in aged rats produced a significant increase in [3H]flunitrazepam binding to the cortex, caudate/putamen and accumbens, and it tended to decrease the [3H]muscimol binding. These results suggest that the selective reduction of specific [3H]muscimol binding in the brain may be responsible, at least in part, for anxiety-related behavior in aged rats. Furthermore, it appears that the significant increase in specific [3H]flunitrazepam binding produced in the brains of aged rats by the long-term administration of KKT may be responsible for the anxiolytic effects of this agent.
我们使用体外定量放射自显影技术,研究了长期给予加味归脾汤(KKT)对年轻和老年大鼠大脑中[3H]蝇蕈醇和[3H]氟硝西泮特异性结合的影响。与年轻大鼠相比,老年大鼠所有检测脑区的[3H]蝇蕈醇特异性结合均降低,而[3H]氟硝西泮结合在任何脑区均未改变。Scatchard分析显示,与年轻大鼠相比,老年大鼠皮质和丘脑中[3H]蝇蕈醇结合位点的最大数量显著减少,但其亲和力保持不变。年轻大鼠长期给予KKT对[3H]蝇蕈醇或[3H]氟硝西泮结合均无影响。相反,老年大鼠进行相同处理后,[3H]氟硝西泮与皮质、尾状核/壳核和伏隔核的结合显著增加,且[3H]蝇蕈醇结合有减少趋势。这些结果表明,大脑中特异性[3H]蝇蕈醇结合的选择性降低可能至少部分导致了老年大鼠的焦虑相关行为。此外,长期给予KKT使老年大鼠大脑中特异性[3H]氟硝西泮结合显著增加,这可能是该药物抗焦虑作用的原因。