CORTICAL INDUCTION OF C-FOS BY INTRASTRIATAL ENDOTHELIN-1 IS MEDIATEDVIA NMDA RECEPTORS

ENDOTHELIN (ET) is a potent vasoconstrictor which has also been propos ed to act as a neuromodulator. We have investigated the action of ET-1 on neurones in vivo, using c-fos as a marker of neuronal activation. Intrastriatal injection of ET-1 caused seizures and barrel rolling whi ch were prevented by pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and attenuated by the nitric-oxide synthas e inhibitor N-omega-nitro-L-arginine (L-NNA). In association with thes e behaviours, a dramatic increase in c-fos mRNA expression was seen in the cerebral cortex. This increase was blocked by both MK-801 and L-N NA. We suggest that ET-1 modulates the activity of cortical afferents to the striatum, and causes seizures via an NMDA receptor-dependent me chanism.