THE dopamine transporter (DAT) is the site at which the neurotoxic met
abolite of MPTP gains access to midbrain dopaminergic (DA) neurons. Ho
wever, not all midbrain DA neurons degenerate following MPTP treatment
. The midbrain DA neurons that contain the calcium-binding protein, ca
lbindin-D-28k (CALB), are relatively invulnerable to MPTP toxicity, co
mpared with DA neurons that lack CALB. Using in situ hybridization and
immunocytochemical staining techniques in the rat and mouse, we now r
eport that there is as much as 10 fold less DAT mRNA in regions where
DA neurons contain CALB compared with regions where DA neurons lack CA
LB. These data suggest that specific midbrain DA neurons are invulnera
ble to MPTP toxicity not only because they contain CALB, but also beca
use they have relatively low DAT activity.