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Brain Res Rev. 2008 Aug;58(2):340-53. Epub 2007 Oct 26.

Glutamate-dopamine-GABA interactions in the aging basal ganglia.

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Department of Physiology, Faculty of Medicine, Universidad Complutense, Ciudad Universitaria, s/n 28040 Madrid, Spain.


The study of neurotransmitter interactions gives a better understanding of the physiology of specific circuits in the brain. In this review we focus mostly on our own results on the interaction of the neurotransmitters glutamate, dopamine and GABA in the basal ganglia during the normal process of aging. We review first the studies on the action of endogenous glutamate on the extracellular concentrations of dopamine and GABA in the neostriatum and nucleus accumbens during aging. It was found that there exists an age-related change in the interaction of glutamate, dopamine and GABA and that these effects of aging exhibit a dorsal-to-ventral pattern of effects with no changes in the dorsal parts (dorsal striatum) and changes in the most ventral parts (nucleus accumbens). Second we reviewed the data on the effects of different ionotropic and metabotropic glutamate receptor agonists on the extracellular concentrations of dopamine and GABA in the nucleus accumbens. The results obtained clearly show the different contribution of each glutamate receptor subtype in the age-related changes produced on the interaction of glutamate, dopamine and GABA in this area of the brain. Third the effects of an enriched environment on the action of AMPA and NMDA-receptor agonists in the nucleus accumbens of rats during aging are also evaluated. Finally, and since the nucleus accumbens has been suggested to play a role in emotion and motivation and also motor behaviour, we speculated on the possibility of a specific contribution for the different glutamatergic pathways terminating in the nucleus accumbens and their interaction with a decreased dopamine playing a relevant role in motor behaviour during aging.

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