Effect of aging on dopaminergic receptors and uptake sites in the rat brain studied by receptor autoradiography.

ABSTRACT

We studied the age-related alterations of dopaminergic receptors in the brain of Fisher 344 rats with various age (3 weeks and 6, 12, 18 and 24 months) using in vitro receptor autoradiography. [3H]SCH 23390, [3H]spiperone and [3H]nemonapride, and [3H]mazindol were used to label dopamine D1 receptors, dopamine D2 receptors and dopamine uptake sites, respectively. In immature rats (3 weeks old), [3H]SCH 23390 binding showed a significant increase in most brain regions compared to adult animals (6 months old), whereas [3H]spiperone and [3H]nemonapride bindings showed no significant alteration in any brain areas. In contrast, [3H]mazindol binding showed a significant decline in most brain regions. On the other hand, the age-related alterations in [3H]SCH 23390 binding were not observed in any brain regions. [3H]Spiperone and [3H]nemonapride bindings also showed no significant alteration in the brain during aging, except for a transient alteration in [3H]spiperone binding in the nucleus accumbens and hippocampus of 12 months old rats. However, [3H]mazindol binding showed a significant reduction in most brain areas of 12 months old rats. Thereafter, the age-related reduction in [3H]mazindol binding was observed in most brain regions of 18 and 24 months old rats. The results demonstrate that dopamine uptake sites are more susceptible to the aging process than both dopamine D1 and D2 receptors. Furthermore, our results suggest that dopaminergic receptors and dopamine uptake sites may develop with different patterns and speeds after birth. Our studies may provide valuable information concerning the effect of aging on dopaminergic systems.