A Critical Evaluation of Influence of Ethanol and Diet on Salsolinol Enantiomers in Humans and Rats

Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Alcoholism Clinical and Experimental Research (Impact Factor: 3.21). 11/2009; 34(2):242-50. DOI: 10.1111/j.1530-0277.2009.01087.x
Source: PubMed


(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.
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).
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.
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.

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Available from: Vijay A Ramchandani
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    • "Early studies suggested that salsolinol might have a role in psychopharmacological effects of ethanol (Davis & Walsh 1970; Davis et al. 1970) and the relationship between these two compounds has long been debated (Lee et al. 2010; Correa et al. 2012; Hipólito et al. 2012; Deehan, Brodie & Rodd 2013). Indeed, brain salsolinol quantification following in vivo ethanol administration is still an unresolved issue (Lee et al. 2010). Accordingly, salsolinol also found in chocolate (Melzig et al. 2000), bananas (Riggin, McCarthy & Kissinger 1976) and alcoholic beverages (Duncan & Smythe 1982), shows poor ability to cross blood brain barrier (Eriksson & Sippel 1977; Origitano, Hannigan & Collins 1981; Correa et al. 2012). "
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    • "Several studies have sought to quantify SAL levels within the body and brain following EtOH ingestion with mixed results. Specifically in the rodent brain, studies have shown that EtOH exposure (via oral consumption or experimenter administered EtOH) increased (Rojkovicova et al., 2008) or did not alter (Lee et al., 2010) SAL levels in several brain regions. Nonetheless, there is a substantial amount of evidence suggesting that SAL is intricately involved with the rewarding properties of EtOH. "
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