Establishment of L-3,4-Dihydroxyphenilalaninde-induced pharmacological dementia model mouse.

Abstract

L-3,4-Dihydroxyphenilalaninde (L-DOPA), through its decarboxylation to dopamine, has been used as the most effective therapy for treatment of Parkinson's disease (PD). Despite almost 30 years of clinical experience, doubts remain as to whether L-DOPA has an adverse effect of causing neuronal injury. We therefore examined the effects of L-DOPA on the learning ability of mice in a step-through passive avoidance task. Orally administrated L-DOPA (10-1000 mg/kg) induced irrecoverable cognitive impairment in C57BL/6N mice. The effect of L-DOPA had dose and time dependency. In contrast, D-3,4-Dihydroxyphenilalaninde, which does not pass through the blood-brain barrier, had no effect. These experiments suggest that L-DOPA immediately affected the brain and caused memory deficit. The findings indicate that L-DOPA-treated mice are able to act as a new model for human dementia.

• Authors: N Itokazu, K Yamamoto, Y Ouchi, J Cyong
• Journal: Neuroscience letters (Neurosci Lett) Vol. 305 Issue 2 Pg. 123-6 (Jun 08 2001) ISSN: 0304-3940 [Print] Ireland
• PMID: 11376899 (Publication Type: Journal Article)

Chemical References

• Antiparkinson Agents
• Levodopa

Topics

• Administration, Oral
• Animals
• Antiparkinson Agents (administration & dosage, pharmacology)
• Avoidance Learning (drug effects)
• Cognition Disorders (chemically induced)
• Dementia (chemically induced)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Levodopa (administration & dosage, pharmacology)
• Male
• Memory Disorders (chemically induced)
• Mice
• Mice, Inbred C57BL
• Stereoisomerism