Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA: implication for L-DOPA-induced dyskinesia in Parkinson's disease.
The medial globus pallidus plays a crucial role in generation of L-DOPA-induced dyskinesia in patients with Parkinson's disease. The 6-hydroxydopamine-lesioned rat exhibiting behavioral sensitization to L-DOPA is one useful animal model for examining L-DOPA-induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6-hydroxydopamine-lesioned rats treated with L-DOPA were examined. Intermittent L-DOPA treatment induced hypertrophy of the lesioned-side of medial globus pallidus and substantia nigra reticulata of 6-hydroxydopamine-lesioned rats with behavioral sensitization to L-DOPA. Additionally, coadministration of a 5-HT1A receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin with L-DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L-DOPA in 6-hydroxydopamine-lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L-DOPA-induced dyskinesia in patients with Parkinson's disease.
Tomiyama
Masahiko
M
Third Department of Medicine, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan. tomiyama@cc.hirosaki-u.ac.jp
Mori
Fumiaki
F
Kimura
Tamaki
T
Ichinohe
Noritaka
N
Wakabayashi
Koichi
K
Matsunaga
Muneo
M
Baba
Masayuki
M
D000818:Animals; D020820:Dyskinesias / Q000188:drug therapy / Q000473:pathology*; D005917:Globus Pallidus / Q000187:drug effects / Q000473:pathology*; D006984:Hypertrophy / Q000473:pathology; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*
D007980:Levodopa; D016627:Oxidopamine