Document Detail

Characterization of the in vivo action of (R)-salsolinol, an endogenous metabolite of alcohol, on serotonin and dopamine metabolism: a microdialysis study.
MedLine Citation:
PMID:  8050034     Owner:  NLM     Status:  MEDLINE    
Using a microdialysis-HPLC technique in conscious rats, we examined the action of (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, (R)-salsolinol (R-Sal), a possible endogenous metabolite of alcohol, on serotonin (5-HT) and dopamine (DA) metabolism in four regions of the brain: the striatum, the substantia nigra, the hippocampus and the hypothalamus. Following 1 mM R-Sal perfusion, the dialysate level of 5-HT in the striatum markedly increased from non-detectable levels to 4259.2 +/- 617.5 nM, while DA increased from 3.4 +/- 0.9 nM to 206.0 +/- 56.5 nM. This increase was one order of magnitude larger in 5-HT than in DA. Conversely, the output of 5-hydroxyindoleacetic acid decreased markedly to non-detectable levels, while 3,4-dihydroxyphenylacetic acid and homovanillic acid outputs decreased below 40% of basal levels. These effects were dose-related to R-Sal (1 microM to 1 mM) and were confirmed also in 3 other brain regions. The R-Sal-induced responses in the striatum were observed even after pretreatment of 2 microM tetrodotoxin, a blocker of nerve-firing activity, via the dialysis membrane. The repetitive perfusion with 1 mM R-Sal into the striatum induced the reproducible response of 5-HT and DA. Furthermore, the potencies of 1 mM R-Sal to increase the output of 5-HT and DA were approximately 783.0-fold and 2.6-fold stronger, respectively, than those of the same dose of methamphetamine. The results suggest that R-Sal acts to stimulate a release of monoamines, 5-HT preferentially, with inhibition of monoamine oxidase and catechol-O-methyltransferase activities.
D Nakahara; W Maruyama; H Hashiguti; M Naoi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  644     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1994 May 
Date Detail:
Created Date:  1994-09-08     Completed Date:  1994-09-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  226-32     Citation Subset:  IM    
Department of Psychology, Nagoya University College of Medical Technology, Japan.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Biogenic Monoamines / metabolism
Brain Chemistry / drug effects*
Catecholamines / metabolism,  physiology
Chromatography, High Pressure Liquid
Dopamine / metabolism*,  physiology
Ethanol / metabolism*
Isoquinolines / pharmacology*
Methamphetamine / pharmacology
Neurons / metabolism
Rats, Wistar
Serotonin / metabolism*,  physiology
Reg. No./Substance:
0/Biogenic Monoamines; 0/Catecholamines; 0/Isoquinolines; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 50-67-9/Serotonin; 525-72-4/salsolinol; 537-46-2/Methamphetamine; 64-17-5/Ethanol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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