Microdialysis studies of D-amphetamine-evoked striatal dopamine overflow in young versus aged F344 rats: Effects of concentration and order of administration

In order to measure the effects of different concentrations of D-amphetamine (D-AMPH) infusions on striatal dopamine (DA) overflow in young versus aged rats, and to determine the influence of preceding infusions on subsequent stimuli, two microdialysis studies were conducted. In the first study, D-AMPH (100, 200, and 2000 μM) was infused in ascending order of concentration, while in the second study the order of administration was reversed. The order of administration significantly affected DA overflow and extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC). Generally, DA overflow was greater for a given concentration when it was administered first in a sequence than when it was administered later in a sequence. The two age groups did not differ on measures of DA overflow. The order of administration also significantly influenced the effect of D-AMPH on extracellular DOPAC, as the D-AMPH-related decreases in DOPAC were greater for a concentration when it was administered earlier versus later in the sequence. This effect was greater in the young rats than in the aged rats. D-AMPH also resulted in diminished levels of DOPAC in the aged rats compared to the young rats. These results suggest that between-groups studies may be more appropriate for determining the effects of different concentrations of D-AMPH on striatal DA overflow. They also demonstrate that while some measures of stimulus-evoked DA overflow may not differ between young and aged F344 rats, extracellular regulation of striatal DA (as measured by changes in DOPAC) may be altered. These alterations may contribute to age-related decreases in motor function.