Characterization of the in vivo action of (R)-salsolinol, an endogenous metabolite of alcohol, on serotonin and dopamine metabolism: a microdialysis study

Brain Res. 1994 May 2;644(2):226-32. doi: 10.1016/0006-8993(94)91684-5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Biogenic Monoamines / metabolism
  • Brain Chemistry / drug effects*
  • Catecholamines / metabolism
  • Catecholamines / physiology
  • Chromatography, High Pressure Liquid
  • Dopamine / metabolism*
  • Dopamine / physiology
  • Ethanol / metabolism*
  • Isoquinolines / pharmacology*
  • Male
  • Methamphetamine / pharmacology
  • Microdialysis
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism*
  • Serotonin / physiology

Substances

  • Biogenic Monoamines
  • Catecholamines
  • Isoquinolines
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Ethanol
  • Methamphetamine
  • salsolinol
  • Dopamine