A fetal nigral graft prevents behavioral supersensitivity associated with repeated injections of L-dopa in 6-OHDA rats. Correlation with D1 and D2 receptors.
The effect of repeated administration of L-3,4-dihydroxyphenylalanine was studied behaviorally and biochemically in grafted versus non-grafted rats with a 6-hydroxydopamine unilateral lesion of the dopaminergic nigro-striatal pathway. Non-grafted rats receiving 14 injections of L-3,4-dihydroxyphenylalanine increased their contraversive circling while grafted rats did not, even after fourteen injections. The density of striatal dopamine receptors was examined by autoradiography using the ligands [3H]-SCH 23390 for dopamine D1 receptors and [3H]-spiperone for D2 receptors. In rats with a lesion of the nigro-striatal dopaminergic pathway, an increase of [3H]-SCH 23390 and [3H]-spiperone binding in the lesioned striatum was observed when compared with the striatum on the intact side. Chronic treatment with L-3,4-dihydroxyphenylalanine led to a further increase in D1 receptor density in the lesioned as well as the intact side. A similar pattern was observed for D2 receptors although the change did not reach significance. A graft of fetal nigral neurons brought the density of both D1 and D2 receptors on the lesioned side back to the level of the intact side. This is observed both in acutely or chronically L-3,4-dihydroxyphenylalanine treated rats. This study suggests that nigral grafts protect the striatum against L-3,4-dihydroxyphenylalanine-induced supersensitivity. It appears that the graft preserves the symmetry of the striatum even though there is an increase of D1 dopamine receptors. These results suggest that a fetal nigral graft could prevent the induction of 3-4-dihydroxyphenylalanine- induced dyskinesia in parkinsonian patients.
Rioux
L
L
Department of Pharmacology, Faculty of Medicine, Laval University, Québec, Canada.
Gagnon
C
C
Gaudin
D P
DP
Di Paolo
T
T
Bédard
P J
PJ
D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D007980:Levodopa / Q000633:toxicity*; D008636:Mesencephalon / Q000637:transplantation; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000502:physiology / Q000637:transplantation*; D010052:Ovariectomy; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology / Q000637:transplantation*
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D007980:Levodopa; D016627:Oxidopamine