Suppressive effect of L-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine.
Ever since the introduction of levo-3,4-dihydroxyphenylalanine (L-dopa) for the treatment of Parkinson's disease, there has been concern that it might accelerate the degeneration of dopamine neurones. Using rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB), we have studied the effect of chronic L-dopa treatment on the survival of dopamine cells which remain in the ventral tegmental area (VTA) ipsilateral to a 6-OHDA lesion. Following lesion surgery, rats were treated with L-dopa and carbidopa administered in the drinking water for 27 weeks. At the end of the treatment period, the number of dopamine cells remaining in each of the lesioned and intact substantia nigra (SN) and VTA were assessed, using tyrosine hydroxylase immunohistochemistry. Chronic L-dopa treatment resulted in an apparent reduction in the number of dopamine neurones remaining in the VTA ipsilateral to the lesion, whereas it had no effect on the number of dopamine cells remaining in the intact SN and VTA. This finding suggests a possible suppressive effect in vivo of L-dopa on dopamine cells in the midbrain of adult animals that have been previously exposed to 6-OHDA.
Blunt
S B
SB
Parkinson's Disease Society Experimental Research Laboratories, King's College, London, England.
Jenner
P
P
Marsden
C D
CD
D000818:Animals; D002230:Carbidopa / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D011954:Receptors, Dopamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D002230:Carbidopa; D004298:Dopamine