Impairment of skill learning ability induced by two types of depletion of dopamine supply from the nigrostriatal system in rats

概要

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Objectives : It is still uncertain whether motor symptoms and learning disorders observed in various dopa-responsive motor disorders depend on the cause of dopamine (DA) depletion or the degree of DA depletion. To answer this question, we produced two animal models with different types of disruption of DA supply in the striatum. Materials and Methods : Intranigral injection of antisense oligonucleotides against synaptotagmin I (syt-AS), a regulator of transmitter release, or intrastriatal injection of 6-hydroxydopamine (6-OHDA) was performed to cause disruption of DA release from the nigrostriatal system in the rats. Results : The 6-OHDA-treated rats displayed a severe disruption of the methamphetamine-induced DA release in the striatum and a severe impairment of the skill learning ability in a rotarod task, while the syt-AS-treated rats exhibited a moderate disruption of the drug-induced release of striatal DA and a mild deficit of the skill learning ability. Conclusion : The severity of impairment of the skill learning ability depends on the degree of DA depletion in the striatum but not on the cause of DA depletion.
北里大学の論文
2006-09-30