PRETREATMENT WITH NIMODIPINE PREVENTS MPTP-INDUCED NEUROTOXICITY AT THE NIGRAL, BUT NOT AT THE STRIATAL LEVEL IN MICE

THE present study assessed the effects of pretreatment with the calciu m-L-type channel blocker nimodipine on biochemical and histological pa rameters of systemic MPTP-induced (2 x 40 mg kg(-1) body weight subcut aneously, 16 h apart), dopaminergic neurotoxicity in black C57BL/6 mic e. Continuous administration of nimodipine via subcutaneously implante d pellets (10 mg), starting 7 days before administration of MPTP, did not antagonize the striatal MPTP-induced dopamine depletion (caudate-p utamen: 80% of control; nucleus accumbens; 25% of control), but almost completely prevented the MPTP-induced tyrosine hydroxylase immunoreac tive-cell loss in the substantia nigra (20% of control) 7 days after a dministration of MPTP. This data suggests that pretreatment with nimod ipine-during the observation period of 7 days-protects against MPTP-in duced neurotoxicity in mice at the nigral ('cell body'), but not at th e synaptic striatal level.