Segovia G, Del Arco A, Mora F
Department of Physiology, Faculty of Medicine, Universidad Complutense, Madrid, Spain.
J Neurochem. 1999 Nov;73(5):2063-72.
The aim of the present study was to investigate, using microdialysis, the effects of aging on the glutamate/dopamine/GABA interaction in striatum and nucleus accumbens of the awake rat. For that, the effects of an increase of the endogenous concentration of glutamate on the extracellular concentration of dopamine and GABA in striatum and nucleus accumbens of young (2-4 months), middle-aged (12-14 months), aged (27-33 months), and very aged (37 months) male Wistar rats were studied. Endogenous extracellular glutamate was selectively increased by perfusing the glutamate uptake inhibitor L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC) through the microdialysis probe. In young rats, PDC (1, 2, and 4 mM) produced a dose-related increase of dialysate concentrations of glutamate in both striatum and nucleus accumbens. PDC also increased dialysate dopamine and GABA in both structures. These increases were significantly correlated with the increases of glutamate but not with the PDC dose used, which strongly suggests that the increases of dopamine and GABA were produced by glutamate. In striatum, there were no significant differences in the dopamine/glutamate and GABA/glutamate correlations between young and aged rats. This means that the effects of glutamate on dopamine and GABA do not change during aging. On the contrary, in the nucleus accumbens of aged rats, the increases of dopamine, when correlated with the increases of glutamate, were significantly lower than in young rats. Moreover, the ratio of dopamine to glutamate increases at maximal increases of glutamate was negatively correlated with aging. On the contrary, the ratio of GABA to glutamate increases in nucleus accumbens was positively correlated with aging, which suggests that the effects of endogenous glutamate on GABA tend to be higher in the nucleus accumbens of aged rats. The findings of this study suggest that aging changes the interaction between endogenous glutamate, dopamine, and GABA in nucleus accumbens, but not in striatum, of the awake rat.
本研究的目的是利用微透析技术，研究衰老对清醒大鼠纹状体和伏隔核中谷氨酸/多巴胺/γ-氨基丁酸（GABA）相互作用的影响。为此，研究了年轻（2 - 4个月）、中年（12 - 14个月）、老年（27 - 33个月）和极老龄（37个月）雄性Wistar大鼠纹状体和伏隔核中，内源性谷氨酸浓度升高对多巴胺和GABA细胞外浓度的影响。通过微透析探针灌注谷氨酸摄取抑制剂L-反式-吡咯烷-3,4-二羧酸（PDC），选择性增加内源性细胞外谷氨酸。在年轻大鼠中，PDC（1、2和4 mM）使纹状体和伏隔核中谷氨酸的透析液浓度呈剂量相关增加。PDC还增加了这两个结构中的透析液多巴胺和GABA。这些增加与谷氨酸的增加显著相关，但与所用的PDC剂量无关，这强烈表明多巴胺和GABA的增加是由谷氨酸引起的。在纹状体中，年轻大鼠和老年大鼠之间多巴胺/谷氨酸和GABA/谷氨酸的相关性没有显著差异。这意味着衰老过程中谷氨酸对多巴胺和GABA的作用没有改变。相反，在老年大鼠的伏隔核中，与谷氨酸增加相关的多巴胺增加显著低于年轻大鼠。此外，谷氨酸最大增加时多巴胺与谷氨酸的比值增加与衰老呈负相关。相反，伏隔核中GABA与谷氨酸的比值增加与衰老呈正相关，这表明老年大鼠伏隔核中内源性谷氨酸对GABA的作用往往更高。本研究结果表明，衰老改变了清醒大鼠伏隔核中内源性谷氨酸、多巴胺和GABA之间的相互作用，但纹状体中没有改变。
