USE OF [H-3] GBR12935 TO MEASURE DOPAMINERGIC NERVE-TERMINAL GROWTH INTO THE DEVELOPING RAT STRIATUM

In this study we determined the temporal association between the appearance of the dopamine transporter, measured by 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine ([H-3]-GBR12935), a potent and selective inhibitor of dopamine uptake, and other biochemical markers of dopaminergic nerve terminal growth into the developing striatum. [H-3]-GBR12935 binding was minimally detected in the rudimentary striatum of embryonic day 14 rat brains, increased to 23% of the adult level by birth, and reached the adult level during the fifth postnatal week. This finding contrasts with a slower developmental increase in [H-3]-dopamine uptake, a functional measure of the transporter. Tyrosine hydroxylase activity levels followed a developmental curve similar to that of [H-3]-GBR12935 binding but did not reach adult levels until the 7th postnatal week. Dopamine content increased at a slower rate, being only 10% and 92% of the adult level at birth and postnatal week 8, respectively. These results indicate that the appearance of a structural, but not optimally functional, dopamine transporter may be the earliest detectable biochemical index of dopaminergic nerve terminal growth into the striatum during development.