Excitotoxic lateral pallidotomy does not relieve L-dopa-induced dyskinesia in MPTP parkinsonian monkeys.
We attempted to relieve the marked overactivity known to occur in the lateral segment of the globus pallidus (GPL) in L-DOPA-induced dyskinesia (LID) by unilateral stereotaxic ibotenic acid lesioning of the GPL in 4 monkeys with MPTP-induced parkinsonism. Two already dyskinetic animals were pallidotomized to counteract LID once established, while 2 L-DOPA-naive MPTP-treated animals were pallidotomized before L-DOPA was ever administered in an attempt to prevent the development of the process conductive to LID. Acutely after the lesion, more prominent akinesia (particularly in the contralateral limbs) with contraversive body deviation and circling behavior were seen for 48 h. Flexor posturing of the contralateral forelimb persisted to a variable degree. When L-DOPA treatment was resumed or instituted 1 week postoperatively, ipsiversive circling behavior occurred in all animals and contralateral dyskinesia worsened in 3, whether L-DOPA or a selective dopamine D2 agonist was administered. Lesions in these 3 cases were fairly restricted to the GPL histologically. One monkey kept L-DOPA-naive before pallidotomy never developed LID contralaterally to the lesion despite treatment for several months. The lesion this time involved the entire GP. The fact that ablation of the GPL worsened LID suggests that a complex rearrangement of the balance of functional capacity between the GP and the subthalamic nucleus takes place in LID which is not amenable to correction merely by a lateral pallidotomy. Our observations also suggest that functional redundancy exists in striatopallidal circuits and that no single pathway is responsible for LID.
Neurobiology Research Centre, Hôpital de l'Enfant-Jésus, Québec, Canada.
P J
PJ
Blanchet
R
R
Boucher
P J
PJ
Bédard
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D005260:Female; D005917:Globus Pallidus / Q000503:physiopathology* / Q000601:surgery; D007980:Levodopa; D008252:Macaca fascicularis; D010302:Parkinson Disease, Secondary / Q000209:etiology / Q000503:physiopathology*
D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine