In vivo electrochemical studies of dopamine diffusion and clearance in the striatum of young and aged Fischer-344 rats

Abstract

Dopaminergic neurons are vulnerable to the degenerative effects of the aging process. Age-dependent functional changes which occur in nigrostriatal and mesolimbic DA pathways may decrease the ability of these systems to effectively communicate with postsynaptic targets, thereby impairing the normal flow of motor information through the basal ganglia. In order to overcome these effects, the brain relies on homeostatic mechanisms which act to balance neurochemical changes. In this study we have tested the hypothesis that dopamine neurons compensate for age-related decreases in depolarization-induced transmitter overflow by altering the rate of DA clearance from the extracellular space. The diffusion and clearance of DA was directly measured in urethane anesthetized Fischer 344 rats using high-speed (5 Hz) in vivo electrochemical recordings and local drug application techniques. The results show that aged rats (24 and 30 months old) are as effective in removing exogenously applied dopamine from the striatum as young rats (6 months old). However, the uptake sites in the aged animals were less responsive to nomifensine, a competitive inhibitor of DA uptake. This drug did not modulate the amplitude of DA signals in the dorsal striatum of 30-month-old rats nor in the ventral striatum of 24-and 30-month-old rats. We can conclude that there are changes in the high affinity uptake carrier based on the different pharmacological actions of nomifensine in the young and aged striatum. If this is the case, then more studies are necessary to determine if drugs used in the treatment of depression (which have the same mechanism of action as nomifensine) are less effective in elderly patients. This research may also lead to the understanding of mechanisms which compensate for age-related deficits in chemical signalling.