Sprouting of striatal serotonin nerve terminals following selective lesions of nigro-striatal dopamine neurons in neonatal rat.
The effects of neonatal intracisternal 6-hydroxydopamine (6-OHDA; 50 micrograms) treatment on striatal serotonin (5-HT) nerve terminals in rat have been characterized using histo- and neurochemical methods. The 6-OHDA lesion caused a 60% reduction of striatal dopamine (DA) concentration when analyzed in the adult stage, while 5-HT levels were increased by about 40% and 3H-5-HT uptake in vitro was increased by about 60%. Using computerized image analysis, a marked increase in 5-HT-like immunoreactive terminal density was found in both rostral (+200%) and caudal (+50%) striatum. Pretreatment with the DA uptake blocker amfolenic acid completely counteracted the 6-OHDA-induced alterations in both DA and 5-HT neurons in the striatum, while pretreatment with the noradrenaline uptake blocker desipramine had no significant effects. Regional analysis of 5-HT levels in the CNS after neonatal 6-OHDA treatment or the combined desipramine + 6-OHDA treatment showed no significant effect in any of the brain areas analyzed, apart from the observed 5-HT increase in striatum. It was furthermore observed that the striatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was decreased, while the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio was increased following the 6-OHDA lesion, indicating compensatory mechanisms in turnover of transmitters. These alterations were completely reversed after pretreatment with amfolenic acid. The present results support the view that the 5-HT hyperinnervation following neonatal 6-OHDA treatment is a collateral sprouting response induced by lesioning of the striatal DA neurons.
Luthman
J
J
Department of Histology, Karolinska Institutet, Stockholm, Sweden.
Bolioli
B
B
Tsutsumi
T
T
Verhofstad
A
A
Jonsson
G
G
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D009411:Nerve Endings / Q000502:physiology; D009416:Nerve Regeneration; D009474:Neurons / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013378:Substantia Nigra / Q000473:pathology*
D012701:Serotonin; D004298:Dopamine