Age-Related Decline in Striatal D2-Dopamine Receptors Is Subject to ‘Economic Correction’

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Abstract
We have previously reported a correlation between the number (Bmax) of striatal D2-dopamine receptors in youth and the magnitude of the decrease to the 40th to 60th week of age. This correlation was observed in five inbred strains of mice, which differ over a 2-fold range in youthful Bmax. To determine the extent to which this correlation can predict changes in strains, other than those so far examined, we measured the binding of [3H]spiperone to striatal membranes in two additional strains (MRL/Mp-++ and DBA/2NNia), in one strain previously tested, C57BL/6, but now maintained in pathogen-free conditions (C57BL/6NNia), and in hybrids (C6D2F1) of C57BL/6NNia and DBA/2NNia mice. The results were as expected from the correlation observed with other strains; that is, the magnitude of decline in Bmax with age is correlated with the density of receptors in youth. To test the stability of these age-related changes, we examined the effect of feeding diets with high (4.5) and low (0.2) polyunsaturated to saturated fatty acid (P/S) ratios to SJL/J and MRL/Mp-++ mice and found both receptor density and affinity and their age-related change to be independent of the dietary P/S ratio. In conclusion, our data are consistent with ‘economic correction’, i.e. with a direct correlation between youthful quantity of striatal D2-dopamine receptors and subsequent extent of decrease with aging.

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