Expression of c-FOS in the brain after activation of L-type calcium channels.

In rodents, administration of the L-type calcium channel activators, +/-Bay K 8644 and FPL 64176, causes an unusual neurobehavioral syndrome that includes dystonia and self-injurious biting. To determine the regional influence of these drugs in the brain, the induction of c-FOS was mapped after administration of these drugs to mice. In situ hybridization with an antisense riboprobe directed to c-FOS mRNA revealed widespread induction, with the highest levels in the striatum, cortex, hippocampus, locus coeruleus, and cerebellum. The induction of c-FOS mRNA was dose dependent, reached maximal expression approximately 60 min after drug treatment, and could be blocked by pretreatment with the L-type calcium channel antagonist, nifedipine. Immunohistochemical stains with an antibody directed to c-FOS protein revealed a pattern of induction similar to that obtained with in situ hybridization in most brain regions. These results demonstrate a very heterogeneous influence of L-type calcium channel activation in different brain regions, despite the nearly universal expression of these channels implied by more classical anatomical methods.