6-하이드록시도파민으로 유도된 흰쥐 뇌내의 도파민 고갈에 대한 l-디프레닐의 억제효과

l-Deprenyl (Selegiline) Prevents 6-Hydroxydopamine-induced Depletion of Dopamine and Its Metabolites in Rat Brain)

Whereas a selective inhibitor of mmoamine oxidase type B, l-deprenyl (selegiline), is now widely used in the treatment of Parkinson`s disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of l-deprenyl against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA). The changes in tissue contents of dopamine, serotmine (5-HT) and their metabolites by l-deprenyl were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (I.p.) admimistration of l-deprenyl showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10mg/kg). The repeated administration of l-deprenyl (0.25 and 1mg/kg, I.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (I.c.v.) infusion of 6-OHDA (100mcg/10mcl/hemisphere) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with l-deprenyl before 6-OHDA administration, the striatal and septal dopamine levels were signaficantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of l-deprenyl also significantly enhanced the dopamine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a l-deprenyl pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.