Excitotoxicity plays a role in the death of tyrosine hydroxylase-immunopositive nigral neurons cultured in serum-free medium

We studied the effects of different amino acid receptor antagonists and a c alcium (Ca2+) channel blocker on the survival of embryonic tyrosine hydroxy lase (TH)-immunopositive nigral neurons grown under serum-free culture cond itions. Ventral mesencephalic neurons mere cultivated for 2 or 7 days. Foll owing serum withdrawal on day 2, some cultures were treated with different concentrations of the noncompetitive N-methyl-D-aspartate (NMDA) receptor a ntagonist dizocilpine hydrogen maleate (MK-801), the competitive NMDA recep tor antagonist 2-amino-5-phosphono-pentanoic acid, the competitive kainate/ quisqualate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione, and the C a2+ channel blocker flunarizine. Treatment with MK-801 or flunarizine incre ased the survival of TH-positive neurons after serum deprivation. These fin dings suggest a possible role for excitotoxicity in dopaminergic cell death which can be prevented by blocking the NMDA receptor or by inhibiting Ca2 entry through voltage-gated channels. (C) 1999 Academic Press.