Quantitative chiral analysis of salsolinol in different brain regions of rats genetically predisposed to alcoholism

Rojkovicova, Tatiana; Mechref, Yehia; Starkey, Jason A.; Wu, Guangxiang; Bell, Richard L.; McBride, William J.; Novotný, Miloš V.

doi:10.1016/j.jchromb.2008.01.016

Cited by 34 publications

(45 citation statements)

References 33 publications

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“…Except for the work of Haber et al (1996), previous studies on humans found that after acute (Faraj et al, 1989;Rommelspacher et al, 1995) or chronic (Faraj et al, 1989) alcohol drinking salsolinol levels in plasma (and presumably brain) may increase. Indeed, forced chronic ethanol consumption raised salsolinol levels in various brain regions of animals as confirmed by Starkey et al (2006) and Rojkovicova et al (2008), who showed that the pattern of ethanol intake determines how much salsolinol levels in the brain are enhanced. By contrast, it was found that salsolinol levels were elevated in the adrenals but not in the striatum of alcohol-preferring rats after 4 weeks of freechoice alcohol drinking (Haber et al, 1999).…”

Section: Introductionmentioning

confidence: 73%

“…By contrast, it was found that salsolinol levels were elevated in the adrenals but not in the striatum of alcohol-preferring rats after 4 weeks of freechoice alcohol drinking (Haber et al, 1999). Other contradictory findings after ethanol consumption of alcohol-preferring rats are the research of Lee et al (2010) and Rojkovicova et al (2008). Rojkovicova et al observed an increase in salsolinol levels in both the putamen and midbrain; whereas Lee et al saw an increase in neither the striatum nor the nucleus accumbens (NAcc).…”

Section: Introductionmentioning

confidence: 96%

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Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

Xie

Hipólito²,

Zuo³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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Previous studies in vivo have shown that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse. Although opioid receptors, especially the -opioid receptors (MORs), may be involved, the cellular mechanisms mediating the effects of salsolinol have not been fully explored. In the current study, we used whole-cell patch-clamp recordings to examine the effects of salsolinol on dopamine neurons of the ventral tegmental area (VTA) in acute brain slices from Sprague-Dawley rats. Salsolinol (0.01-1 M) dose-dependently and reversibly increased the ongoing firing of dopamine neurons; this effect was blocked by naltrexone, an antagonist of MORs, and gabazine, an antagonist of GABA A receptors. We further showed that salsolinol reduced the frequency without altering the amplitude of spontaneous GABA A receptor-mediated inhibitory postsynaptic currents in dopamine neurons. The salsolinol-induced reduction was blocked by both naltrexone and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, an agonist of MORs. Thus, salsolinol excites VTA-dopamine neurons indirectly by activating MORs, which inhibit GABA neurons in the VTA. This form of disinhibition seems to be a novel mechanism underlying the effects of salsolinol.

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Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 96%

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

Xie

Hipólito²,

Zuo³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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“…Figure 1 illustrates two proposed synthetic pathways of Sal from dopamine and acetaldehyde (AcH). The first one produces the racemic mixture of both enantiomers (Robbins et al 1968;Zhu et al 2008), the latter produces (R)-Sal only Rojkovicova et al 2008). Accordingly, the surplus of (R)-Sal detected in the human brain may be biosynthesized by this putative enzyme.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

et al. 2011

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Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; Sal) is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is supposed to have a role in the development of Parkinson-like syndrome in both human and non-human subjects. In the human brain, the amount of (R)-enantiomer of Sal is much higher than (S )-enantiomer, suggesting that a putative enzyme may participate in the synthesis of (R)-salsolinol, called (R)-salsolinol synthase. In this study, the (R)-salsolinol synthase activity in the condensation of dopamine and acetaldehyde was investigated in the crude extracts from the brains of Sprague Dawley rats. Identification of the enzymatic reaction products and enzyme activity detection were achieved by HPLC-electrochemical detection. The discovery of this enzyme activity in rat's brain indicates the natural existence of (R)-salsolinol synthase in the brains of humans and rats, and it is distributed in most brain regions of rat with higher activity in soluble proteins extracted from striatum and substantia nigra.

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“…In terms of its endogenous identification, it is true that measurements of Sal levels were analytically challenging because of the very low levels of Sal in the brain tissue (Starkey et al 2006) which was also another conflictive aspect. At present, however, sensitive, reliable, and versatile methods for Sal analysis in the brain (Rojkovicova et al 2008;Starkey et al 2006) have been recently developed to further enhance the detection limits and its chiral resolution. With these new methodologies, the authors unequivocally demonstrated that Sal levels increase in several brain areas (nucleus accumbens (NAc), caudate putamen, and midbrain) after very different alcohol drinking procedures.…”

Section: Introductionmentioning

confidence: 99%

Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of μ-opioid receptors

et al. 2010

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Quantitative chiral analysis of salsolinol in different brain regions of rats genetically predisposed to alcoholism

Cited by 34 publications

References 33 publications

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Locomotor stimulant effects of acute and repeated intrategmental injections of salsolinol in rats: role of μ-opioid receptors

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