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.
B
B
Zivkovic
A
A
Oblin
G
G
Bartholini
D000818:Animals; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D013373:Substance P; C017985:progabide; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol