Document Detail

A critical evaluation of influence of ethanol and diet on salsolinol enantiomers in humans and rats.
MedLine Citation:
PMID:  19951298     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: (R/S)-Salsolinol (SAL), a condensation product of dopamine (DA) with acetaldehyde, has been speculated to have a role in the etiology of alcoholism. Earlier studies have shown the presence of SAL in biological fluids and postmortem brains from both alcoholics and nonalcoholics. However, the involvement of SAL in alcoholism has been controversial over several decades, since the reported SAL levels and their changes after ethanol exposure were not consistent, possibly due to inadequate analytical procedures and confounding factors such as diet and genetic predisposition. Using a newly developed mass spectrometric method to analyze SAL stereoisomers, we evaluated the contribution of ethanol, diet, and genetic background to SAL levels as well as its enantiomeric distribution.
METHODS: Simultaneous measurement of SAL enantiomers and DA were achieved by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Plasma samples were collected from human subjects before and after banana (a food rich in SAL) intake, and during ethanol infusion. Rat plasma and brain samples were collected at various time points after the administration of SAL or banana by gavage. The brain parts including nucleus accumbens (NAC) and striatum (STR) were obtained from alcohol-non-preferring (NP) or alcohol-preferring (P) rats as well as P-rats which had a free access to ethanol (P-EtOH).
RESULTS: Plasma SAL levels were increased significantly after banana intake in humans. Consistently, administration of banana to rats also resulted in a drastic increase of plasma SAL levels, whereas brain SAL levels remained unaltered. Acute ethanol infusion did not change SAL levels or R/S ratio in plasma from healthy humans. The levels of both SAL isomers and DA were significantly lower in the NAC of P rats in comparison to NP rats. The SAL levels in NAC of P rats remained unchanged after chronic free-choice ethanol drinking. There were decreasing trends of SAL in STR and DA in both brain regions. No changes in enantiomeric ratio were observed after acute or chronic ethanol exposure.
CONCLUSIONS: SAL from dietary sources is the major contributor to plasma SAL levels. No significant changes of SAL plasma levels or enantiomeric distribution after acute or chronic ethanol exposure suggest that SAL may not be a biomarker for ethanol drinking. Significantly lower SAL and DA levels observed in NAC of P rats may be associated with innate alcohol preference.
Jeongrim Lee; Vijay A Ramchandani; Kei Hamazaki; Eric A Engleman; William J McBride; Ting-Kai Li; Hee-Yong Kim
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2009-11-24
Journal Detail:
Title:  Alcoholism, clinical and experimental research     Volume:  34     ISSN:  1530-0277     ISO Abbreviation:  Alcohol. Clin. Exp. Res.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-18     Completed Date:  2010-02-24     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7707242     Medline TA:  Alcohol Clin Exp Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  242-50     Citation Subset:  IM    
Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
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MeSH Terms
Alcohol Drinking / genetics,  psychology
Biogenic Amines / analysis
Central Nervous System Depressants / pharmacology*
Chromatography, High Pressure Liquid
Dopamine / blood
Ethanol / pharmacology*
Food Analysis
Isoquinolines / blood*,  chemistry
Middle Aged
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Young Adult
Grant Support
AA014437/AA/NIAAA NIH HHS; AA07611/AA/NIAAA NIH HHS; P60 AA007611-200011/AA/NIAAA NIH HHS; R01 AA014437-05/AA/NIAAA NIH HHS; Z01 AA000284-19/AA/NIAAA NIH HHS
Reg. No./Substance:
0/Biogenic Amines; 0/Central Nervous System Depressants; 0/Isoquinolines; 64-17-5/Ethanol; 9ILS801M65/salsolinol

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