Age-related changes in the capacity, rate, and modulation of dopamine uptake within the striatum and nucleus accumbens of Fischer 344 rats: An in vivo electrochemical study

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 ra ts were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ej ected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-m onth old rats. The DA ejections produced larger DA signal amplitudes in the order rats, suggesting age-related differences in the capacity to clear ex tracellular DA. Within the striatum, the capacity and rate of DA uptake wer e reduced by 50% in the aged groups (18 and 24 months) compared with the yo unger rats (6 and 12 months). In the nucleus accumbens, significant reducti ons in DA uptake capacity and rate were observed in the 24-month group. In both brain regions and in all age groups studied, the rate of DA uptake was found to be concentration-dependent until a maximal rate was reached. The maximum rate of DA transport was significantly reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24 months versus 6 and 12 m onths). The ability of nomifensine, an inhibitor of the DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus accumbens was also decreased with age (24 months Versus 6 months). Taken together, these findings demonstrate substantial age-related deficits in DA uptake process es within the striatum and the nucleus accumbens, consistent with the hypot hesis that DA uptake may be slowed in aged animals to compensate for reduct ions in DA release.