Milbrandt J C, Albin R L, Turgeon S M, Caspary D M
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62702, USA.
Neuroscience. 1996 Jul;73(2):449-58. doi: 10.1016/0306-4522(96)00050-4.
The inhibitory neurotransmitter GABA has been shown to be critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the inferior colliculus. Studies in the rat and human inferior colliculus have suggested significant changes in functions related to GABA neurotransmission occur in the aged. These changes include significant decreases in GABA content, GABA release, GABA neurons, glutamate decarboxylase enzymatic activity, and GABAB receptor binding. Such changes within the inferior colliculus may affect the ability of elderly listeners to process complex acoustic signals, particularly in the presence of background noise. The present study was designed to examine the regional distribution and effects of aging on GABAA receptor binding sites in the Fischer 344 rat inferior colliculus using in vitro quantitative receptor autoradiography. [3H]GABA binding to GABAA receptors was significantly reduced in the inferior colliculus of young adult (3 months) and aged (18-26 months) rats when compared to 2-month animals. However, no significant changes were observed after 3 months of age. Single concentrations of tritiated GABAA receptor ligands (muscimol, t-butylbicycloorthobenzoate, and flunitrazepam) revealed no significant age-related changes in receptor binding in the inferior colliculus between 3 and 26 months of age. To characterize further the pharmacology of the GABAA receptor in the inferior colliculus, GABA modulation of the picrotoxin binding site was examined using [3H]t-butylbicycloorthobenzoate. When increasing concentrations of GABA were added to the incubation buffer, a significant decrease in binding was observed in the inferior colliculus of rats in each age group. In aged rats, the dose-response curve was shifted to the left, indicating an increase in the potency of GABA to inhibit [3H]t-butylbicycloorthobenzoate binding. Although no changes in GABAA receptor binding were detected in the inferior colliculus after 3 months of age, a significant alteration in interaction between the GABA and picrotoxin binding sites was observed in the inferior colliculus of aged rats when compared to 3-month-old young adults. This difference appears to reflect an increased sensitivity of the receptor to GABA modulation in aged rats and, thus, may serve as a compensatory mechanism to enhance GABAA receptor function in response to a presynaptic loss of inhibition.
抑制性神经递质γ-氨基丁酸（GABA）已被证明在塑造下丘对简单和复杂听觉刺激的神经元反应中起关键作用。对大鼠和人类下丘的研究表明，与GABA神经传递相关的功能在衰老过程中发生了显著变化。这些变化包括GABA含量、GABA释放、GABA能神经元、谷氨酸脱羧酶活性和GABAB受体结合的显著下降。下丘内的这些变化可能会影响老年听众处理复杂声音信号的能力，尤其是在存在背景噪音的情况下。本研究旨在使用体外定量受体放射自显影技术，研究衰老对Fischer 344大鼠下丘中GABAA受体结合位点的区域分布和影响。与2个月大的动物相比，年轻成年（3个月）和老年（18 - 26个月）大鼠下丘中[3H]GABA与GABAA受体的结合显著减少。然而，3个月龄后未观察到显著变化。单一浓度的氚化GABAA受体配体（蝇蕈醇、叔丁基双环邻苯二甲酸酯和氟硝西泮）显示，3至26个月龄大鼠下丘中受体结合没有与年龄相关的显著变化。为了进一步表征下丘中GABAA受体的药理学特性，使用[3H]叔丁基双环邻苯二甲酸酯研究了GABA对印防己毒素结合位点的调节作用。当向孵育缓冲液中添加浓度不断增加的GABA时，每个年龄组大鼠的下丘中均观察到结合显著减少。在老年大鼠中，剂量反应曲线向左移动，表明GABA抑制[3H]叔丁基双环邻苯二甲酸酯结合的效力增加。尽管3个月龄后在下丘中未检测到GABAA受体结合的变化，但与3个月大的年轻成年大鼠相比，老年大鼠下丘中GABA与印防己毒素结合位点之间的相互作用发生了显著改变。这种差异似乎反映了老年大鼠受体对GABA调节的敏感性增加，因此可能作为一种补偿机制，以增强GABAA受体功能，应对突触前抑制的丧失。
