NMDA modulation of dopamine dynamics is diminished in the aged striatum: An in vivo voltametric study

The technique of in vivo voltametry and a paired recording paradigm were employed to study the age-related changes in N-methyl-d-aspartate (NMDA) function in regulating the striatal dopaminergic transmission in male Sprague-Dawley rats. Microinjection of NMDA (100 pmol) consistently elicited larger striatal dopamine (DA) overflows from young rats (3-4 months old) than from aged rats (27-28 months old). Furthermore, the rate of clearance (Tc) of the NMDA-evoked dopamine release was lower in the aged rats. Local application of dopamine evoked reversible electrochemical signals with similar amplitudes in both young and aged rats. However, Tc was reduced and time course parameters were prolonged in the aged rats. While microejection of NMDA (1 pmol) did not induce any dopamine overflow, simultaneous administration of NMDA and K+ evoked larger dopamine releases than K+ alone in the young striatum. Concomitant application of NMDA did not potentiate the K+-evoked dopamine release in the aged striatum. Taken together, with the reduced dopamine release in response to depolarizing stimuli, our in vivo electrochemical data suggest that age-related changes in NMDA function contribute to the impaired dopaminergic dynamics, including an attenuation of NMDA-evoked dopamine release and a diminished augmentation by K+ of NMDA-induced dopamine release during the normal aging process.