Dopamine--glutamate--GABA interactions and ageing: studies in the striatum of the conscious rat

The effects of apomorphine, a D1-D2 dopamine receptor agonist, on the extracellular concentrations of glutamate and GABA were investigated in the striatum of young, middle-aged and aged rats. In vivo intracerebral perfusions were undertaken in the conscious rat using a concentric push-pull cannula system. Amino acid concentrations in samples were determined by HPLC with fluorometric detection. Apomorphine produced a concentration-related rise in striatal glutamate and GABA concentrations in young rats. Maximal increases were obtained at 20 microM apomorphine, and concentrations reached 184 and 191% of the basal value for glutamate and GABA respectively. Apomorphine failed to produce similar increases in glutamate concentration in middle-aged and aged rats. Apomorphine, at 10 microM, also failed to produce an increase in GABA concentration in the aged rats. However, at 20 microM apomorphine produced increases in GABA concentration in middle-aged and aged rats similar to those produced in young rats. These data are indicative of a change in threshold for GABA release induced by dopamine receptor stimulation in the aged rat. These results indicate that an interaction among dopamine, glutamate and GABA exists in the striatum of the rat, and that this type of interaction deteriorates with age.