Effects of aging on the interaction between glutamate, dopamine, and GABA in striatum and nucleus accumbens of the awake rat

The aim of the present study was to investigate, using microdialysis, the e ffects 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 concentrati on of dopamine and GABA in striatum and nucleus accumbens of young (2-4 mon ths), middle-aged (12-14 months), aged (27-33 months), and very aged (37 mo nths) 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 dialy sate concentrations of glutamate in both striatum and nucleus accumbens. PD C also increased dialysate dopamine and GABA in both structures. These incr eases were significantly correlated with the increases of glutamate but not with the PDC dose used, which strongly suggests that the increases of dopa mine and GABA were produced by glutamate. In striatum, there were no signif icant differences in the dopamine/glutamate and GABA/glutamate correlations between young and aged rats. This means that the effects of glutamate on d opamine and GABA do not change during aging. On the contrary, in the nucleu s accumbens of aged rats, the increases of dopamine, when correlated with t he increases of glutamate, were significantly lower than in young rats. Mor eover, 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 correla ted 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, o f the awake rat.