Inhibition of DT-diaphorase potentiates the in vivo neurotoxic effect of intranigral injection of salsolinol in rats.
The present study shows that intranigral injection of dicoumarol, a DT-diaphorase inhibitor, potentiates the neurotoxic effect of salsolinol (salsolinol 1.25 nmoles plus dicoumarol 2 nmoles; in 2 microl). Rats treated with dicoumarol plus salsolinol presented a characteristic contralateral rotational behaviour when they were stimulated with apomorphine (0.5 mg/kg, s.c.), similar to rats injected unilaterally with 6-hydroxydopamine (6-OHDA). These rats also exhibited impairment of motor and cognitive behaviours. The results support the hypothesis that DT-diaphorase plays a protective role in the nigrostriatal dopaminergic systems.
Díaz-Véliz
G
G
Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Avda. Salvador 486, Casilla 16038 Santiago-9, Chile. gdiaz@med.uchile.cl
Mora
S
S
Lungenstrass
H
H
Segura-Aguilar
J
J
D000818:Animals; D001728:Dicumarol / Q000008:administration & dosage; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D001728:Dicumarol; C036617:salsolinol; D016660:NAD(P)H Dehydrogenase (Quinone)