Establishment of L-3,4-Dihydroxyphenilalaninde-induced pharmacological dementia model mouse.
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.
Itokazu
N
N
Department of Bioregulatory Function, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
Yamamoto
K
K
Ouchi
Y
Y
Cyong
J
J
D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced; D003704:Dementia / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D013237:Stereoisomerism
D000978:Antiparkinson Agents; D007980:Levodopa