Amphetamine neurotoxicity on dopamine nerve terminals in the caudate nucleus of mice

Continuous administration of D-amphetamine to mice by osmotic minipumps (placed s.c.) delivering 25 micrograms/h for 7 days led to significant decreases in the endogenous dopamine concentration (-51%) and [3H]noradrenaline uptake (-43%) in vitro in the caudate nucleus. Fluorescence histochemical analysis demonstrated a marked reduction of dopamine fluorescence as well as catecholamine accumulations (sign of neurotoxicity) in the caudate nucleus. No notable effects were noted on the fluorescence morphology of the dopamine cell bodies in the mesencephalon. The dopamine levels were still significantly reduced (-37%) after two months, while the [3H]noradrenaline uptake had at this time-point reached almost normal values. The results are compatible with the view that D-amphetamine can induce acutely a neurodegenerative damage of central dopamine neurons at the level of the nerve terminals in the caudate nucleus with possibilities for regeneration and recovery in the chronic state.