Document Detail

Altered dopamine and serotonin metabolism in the dopamine-denervated and serotonin-hyperinnervated neostriatum of adult rat after neonatal 6-hydroxydopamine.
MedLine Citation:
PMID:  8071864     Owner:  NLM     Status:  MEDLINE    
3,4-Dihydroxyphenylalanine (L-DOPA), 5-hydroxy-l-tryptophan (5-HTP), dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured in the rostral neostriatum of adult rats neonatally lesioned with 6-hydroxydopamine (6-OHDA) after treatment with NSD-1015 (aromatic L-amino acid decarboxylase inhibitor), pargyline (monoamine oxidase inhibitor) or probenecid (blocker of acidic metabolite efflux). Binding experiments with DA and 5-HT transporter ligands allowed us to relate observed changes to the number of DA and 5-HT terminals. One and 3 months after the lesions were made, DA, 3,4-dihydroxyphenylacetic acid (DOPAC)- and homovanillic acid (HVA)-content as well as [3H]N-[1-(2-benzo(b)-thiophenyl)cyclohexyl]piperidine ([3H]BTCP) binding were lowered to 1% to 2% of control values, reflecting a permanent DA denervation. After 1 month, 5-HT content was increased by 96% and 5-hydroxyindole-3-acetic acid (5-HIAA) was increased by 50% in the presence of control levels of [3H]citalopram binding, suggesting that there was an increased amount of 5-HT per neostriatal 5-HT terminal. At 3 months, 5-HT content had increased by 205%, 5-HIAA remained increased by 50% and [3H]citalopram binding had reached 170% of control values, indicating a persistent increase in 5-HT content within an excessive number of 5-HT terminals (hyperinnervation). At both survival times, neostriatal L-DOPA accumulation after NSD-1015 was low, but ratios of L-DOPA to DA and of L-DOPA to [3H]BTCP were greatly elevated. 5-HTP accumulation was increased, but ratios of 5-HTP to 5-HT were lower than control, despite unchanged ratios of 5-HTP to [3H]citalopram.(ABSTRACT TRUNCATED AT 250 WORDS)
E Molina-Holgado; K M Dewar; L Descarries; T A Reader
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  270     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-28     Completed Date:  1994-09-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  713-21     Citation Subset:  IM    
Département de Physiologie, Faculté de Médecine, Université de Montréal, Quebec, Canada.
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MeSH Terms
Animals, Newborn
Carrier Proteins / metabolism
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins
Membrane Glycoproteins / metabolism
Membrane Transport Proteins*
Monoamine Oxidase Inhibitors / pharmacology
Neostriatum / drug effects,  metabolism*
Nerve Tissue Proteins*
Oxidopamine / pharmacology*
Rats, Sprague-Dawley
Serotonin / metabolism*
Serotonin Plasma Membrane Transport Proteins
Reg. No./Substance:
0/Carrier Proteins; 0/Dopamine Plasma Membrane Transport Proteins; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Monoamine Oxidase Inhibitors; 0/Nerve Tissue Proteins; 0/Serotonin Plasma Membrane Transport Proteins; 0/Slc6a4 protein, rat; 1199-18-4/Oxidopamine; 50-67-9/Serotonin

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