Progabide reverses the nigral substance P reduction induced by chronic impairment of dopaminergic transmission.

Repeated treatment with haloperidol or lesion of nigrostriatal dopaminergic neurons with 6-hydroxydopamine produced a reduction in substance P immunoreactivity in the rat substantia nigra. This reduction was reversed by the repeated administration of progabide, a selective GABA receptor agonist. As GABA inhibits substance P release, these results suggest that the reduction in nigral substance P levels was due to an increased liberation of the peptide probably related to deficient GABAergic function induced by impairment of striatal dopaminergic transmission.