Transplantation of embryonic mesencephalic and medullary raphe neurons to the neostriatum of rats with unilateral 6-hydroxydopamine lesions.
The implantation of dopamine-rich mesencephalic grafts into the 6-hydroxydopamine (6-OHDA)-lesioned neostriatum of rats was accompanied by marked hyperinnervation by serotonin (5-HT) fibers. The purpose of this study was to examine the possibility that the graft-derived 5-HT hyperinnervation is governed by target-related effects present in the host neostriatum and the question of whether grafts rich in 5-HT cells can ameliorate the drug-induced motor asymmetry resulting from unilateral 6-OHDA lesions. Rats were allocated to one of two groups: lesion plus mesencephalic raphe grafts (group R5-HT/L); and lesion plus medullary raphe grafts (group C5-HT/L). A third group, sham-lesion plus mesencephalic raphe grafts (group R5-HT/S) was included. Complete recovery of (+)-amphetamine-induced rotation was observed only in rats which received 5-HT grafts derived from medullary raphe neurons. There was no marked recovery of apomorphine-induced rotation in either of the R5-HT/L and C5-HT/L groups. Immunohistochemistry showed that the R5-HT/L and C5-HT/L groups had 5-HT hyperinnervation in the neostriatum of the lesioned side. There was no target-related effect of the 6-OHDA-lesioned neostriatum specific for the different types of 5-HT tissue. It seems likely that the 5-HT tissue derived from the medullary raphe may contain additional neurotransmitters which contribute to the behavioral recovery.
Parkinson's Disease Society Experimental Research Laboratories, King's College London, UK.
Y
Y
Takeuchi
T
T
Sawada
S
S
Blunt
P
P
Jenner
C D
CD
Marsden
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016332:Fetal Tissue Transplantation; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000502:physiology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000637:transplantation*; D016627:Oxidopamine / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D012701:Serotonin; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine