Effects of chronic reserpine treatment on development of maturity of the putamen in fetal rabbits.

Developing nigrostriatal axons and their perikarya have substantial quantities of dopamine (DA) before the axons reach their postsynaptic target. In order to investigate possible developmental effects of these stores of DA, we have depleted DA chronically during critical periods in the ontogeny of the nigrostriatal system. Reserpine (0.04-0.14 mg/kg/day) was given repeatedly to maternal rabbits for various periods starting before neuroblasts of the substantia nigra first exhibit fluorescence until 2 days before term when the fetuses were sacrificed. Reserpine crossed the placenta and depleted DA in the fetal putamens. Control fetuses had widespread fluorescent axons and terminals. Counts of mature axonal boutons in electron micrographs of the putamen of reserpine-treated fetuses showed that there were 4.3 +/- 0.6 SE/100 microns2, which is less than 1/2 the control value of 10.2 +/- 0.6 SE/100 microns2 (p less than 0.001). The neuropil of the putamen of the reserpine-treated fetus was also less mature; the relative volume occupied by growth cones (40.5% +/- 5.7 SE) was twice that of controls (20.6% +/- 2.4 SE) (p less than 0.005). Although it remains to be shown that the delayed development of both pre- and postsynaptic elements of the nigrostriatal system is specifically related to the known ability of reserpine to deplete DA, the results are consistent with the hypothesis that early stores of DA may be important in developing dopaminergic systems.