Neonatal dopamine-rich grafts and 6-OHDA lesions independently provide partial protection from the adult nigrostriatal lesion syndrome.
Previous studies have shown that neonatally dopamine-depleted rats are subsensitive to dopamine antagonists and do not respond to homeostatic imbalances as adults. This suggests that these animals maintain themselves independent of the dopamine system. If this is so, they should be insensitive to treatment with adult 6-hydroxydopamine (6-OHDA) lesions. Other experiments have shown that dopamine-rich grafts in the neonatal brain will provide some protection from the severe ingestive deficits induced by bilateral 6-OHDA lesions in adulthood. Three groups of animals received either nigra grafts into the intact neonatal brain, neonatal 6-OHDA lesions, or both neonatal 6-OHDA lesions and nigra grafts. A fourth group served as sham-operated controls. Methylamphetamine and haloperidol challenges showed that the neonatally lesioned animals regulated locomotor activity, eating and drinking independent of the dopamine system. Remarkably, however, 80% of these nevertheless showed the full syndrome of aphagia, adipsia and akinesia in response to adult lesions. The grafts into intact group showed enhanced survival in that 36% of the rats were able to maintain themselves following the adult lesion. The graft into neonatally lesioned rats restored their activational response to pharmacological challenges but did not provide any additional protection from the adult lesion. This suggests that different mechanisms underlie the protection against adult nigrostriatal lesions provided by neonatal grafts and neonatal lesions.
Rogers
D C
DC
Department of Experimental Psychology, University of Cambridge, U.K.
Dunnett
S B
SB
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000637:transplantation; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000502:physiology; D009048:Motor Skills / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D008694:Methamphetamine; D016627:Oxidopamine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine