Dopamine neoinnervation in the substantia nigra and hyperinnervation in the interpeduncular nucleus of adult rat following neonatal cerebroventricular administration of 6-hydroxydopamine.
An aberrant network of dopamine axons was found to pervade the rat substantia nigra following neonatal destruction of its dopamine nerve cell bodies and dendrites by cerebroventricular administration of 6-hydroxydopamine. Light-microscopic immunocytochemistry with a primary monoclonal antibody directed against dopamine-glutaraldehyde-protein was used to investigate the time-course of development and the critical period of induction of this ectopic dopamine innervation (neoinnervation). In rats 6-hydroxydopamine-lesioned at postnatal day 3 (P3) and examined at P7, P10, P15, P30 or later, some dopamine fibers were already present in the substantia nigra at P7; their number increased sharply until P15 and only slightly thereafter, assuming a topographic distribution reminiscent of the missing dopamine nerve cell bodies and dendrites. A similar growth of dopamine fibers took place in the substantia nigra after lesions made at P6, P9 and P12, but was less pronounced after lesion at P15 and absent after lesion at P21 or later. Excessive innervation by dopamine axons (hyperinnervation) was concomitantly observed in the nearby interpeduncular nucleus. The sprouting of dopamine axons in both regions was therefore rapid and coincided in time and space with the developmental redistribution of mesencephalic dopamine neurons in normal rat. It is conceivable that these aberrant dopamine innervations play a role in the peculiar behavior and responsiveness to dopaminergic agents manifested by neonatally 6-hydroxydopamine-lesioned rats. It will be of particular interest to investigate the functional consequences of the dopamine neoinnervation in the substantia nigra, where an eventual axonal release might thus be replacing the normal somatodendritic release of this amine.
Fernandes Xavier
F G
FG
Département de pathologie, Faculté de médecine, Université de Montréal, Québec, Canada.
Doucet
G
G
Geffard
M
M
Descarries
L
L
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology
D016627:Oxidopamine; D004298:Dopamine