Nabeshima T, Yamada K, Hayashi T, Hasegawa T, Ishihara S, Kameyama T, Morimasa T, Kaneyuki T, Shohmori T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Life Sci. 1994;55(20):1585-93. doi: 10.1016/0024-3205(94)00320-3.
We used in vitro quantitative autoradiography to investigate changes in neurotransmitter receptor binding, including muscarinic cholinergic, PCP, GABAA, benzodiazepine, D1 and 5-HT2A receptor, in the brains of aged rats, compared with such binding in young rats. Scatchard analysis revealed that the maximal number of binding sites for [3H]quinuclidinyl benzilate (QNB) in the caudate/putamen and accumbens was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. The specific binding of [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) for the ion channels coupled with N-methyl-D-aspartate receptors in the caudate/putamen and hippocampus was significantly decreased in aged rats compared with young rats. The [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding was not changed in any brain regions. The [3H]SCH23390 binding for dopamine D1 receptors was significantly increased in the parietal cortex, but decreased in the caudate/putamen and accumbens of aged rats compared with that in young rats. The [3H]ketanserin binding for 5-HT2A receptors in the cortex and accumbens was significantly decreased in aged rats compared with young rats. These results suggest that uneven changes in receptors for various neurotransmitters throughout the brain may be responsible for the decline of brain function in aged rats.
我们采用体外定量放射自显影技术,研究老年大鼠脑内神经递质受体结合的变化,包括毒蕈碱型胆碱能、苯环己哌啶(PCP)、γ-氨基丁酸A(GABAA)、苯二氮䓬、D1和5-羟色胺2A(5-HT2A)受体,并与年轻大鼠脑内的此类结合情况进行比较。Scatchard分析显示,与年轻大鼠相比,老年大鼠尾状核/壳核及伏隔核中[3H]喹核酯(QNB)的最大结合位点数显著减少,但其亲和力保持不变。与年轻大鼠相比,老年大鼠尾状核/壳核及海马中与N-甲基-D-天冬氨酸受体偶联的离子通道上[3H]N-(1-[2-噻吩基]环己基)3,4-哌啶(TCP)的特异性结合显著减少。与年轻大鼠相比,老年大鼠所有检测脑区中[3H]蝇蕈醇结合均减少,而[3H]氟硝西泮结合在任何脑区均未改变。与年轻大鼠相比,老年大鼠顶叶皮质中多巴胺D1受体的[3H]SCH23390结合显著增加,但尾状核/壳核及伏隔核中则减少。与年轻大鼠相比,老年大鼠皮质及伏隔核中5-HT2A受体的[3H]酮色林结合显著减少。这些结果表明,老年大鼠脑内不同神经递质受体的不均衡变化可能是其脑功能衰退的原因。