Fluoro-Ruby labeling prior to an amphetamine neurotoxic insult shows a definitive massive loss of dopaminergic terminals and axons in the caudate-putamen

Fluoro-Ruby (FR) was injected into the substantia nigra (SNc) to label dopaminergic axons and terminals in the caudate putamen (CPu) of rats 7 days prior to a neurotoxic d-amphetamine (AMPH) exposure. Three days after AMPH exposure, a massive loss in the TH immunoreactive (TH⁺) axons and terminals was seen in the CPu. The FR-labeled (FR⁺) axons and terminals in the CPu were greatly diminished with those remaining being enlarged or swollen after AMPH. Fluoro-Jade C (FJ-C) labeling was used to verify AMPH-induced axonal and terminal degeneration. This study demonstrates that fluorescent anterograde tract tracers can be used to show the subsequent axonal and terminal degeneration after systemic exposures to toxins and provides direct evidence that CPu axons and terminals from SNc dopaminergic neurons can be destroyed after neurotoxic exposure to AMPH.