title: Systematic regional study of dopamine, norsalsolinol, and (R/S)-salsolinol levels in human brain areas of alcoholics.
abstract: BACKGROUND
  Dopamine (DA)-derived tetrahydroisoquinolines (TIQs) are discussed as neurochemical factors of addiction processes in alcoholism. In a prospective study, the regional distribution of DA, (R)-salsolinol (SAL), and (S)-SAL, as well as norsalsolinol (NorSAL) was examined systematically in a large collective of human brain samples obtained by autopsy.
  
  
  METHODS
  The material comprises 44 brains of alcoholics and 47 controls with 6 standardized specimens in each case. The analytes were determined after solid-phase extraction and enantioselective derivatization using gas chromatography-mass spectrometry.
  
  
  RESULTS
  Levels of DA, (R/S)-SAL, and NorSAL in alcoholics did not differ significantly from those of the control group. A relationship between alcohol consumption and SAL formation could not be proved. Topical differences and no ubiquitous occurrence were encountered. Significant amounts of (R)-SAL and (S)-SAL as well as NorSAL only were found in DA-rich areas of the basal ganglia, whereas in other regions of the brain, no TIQs were detected. Especially in the nucleus caudatus, the concentrations of DA, SAL, and NorSAL decreased significantly with rising age.
  
  
  CONCLUSIONS
  These findings do not support the hypothesis that one of the SAL enantiomers or NorSAL is involved in the genesis of alcoholism. However, they suggest that the concentration of the substrate DA may determine the alkaloid level during in vivo formation. The revealed data can serve as reference for other studies in humans concerning the cause of alcoholism or other neurodegenerative diseases with the involvement of TIQs.
authors.affiliation: Institute of Legal Medicine, Rheinische Friedrich-Wilhelms-University, Bonn, Germany. f.musshoff@uni-bonn.de
authors.forename: Frank
authors.initials: F
authors.lastname: Musshoff
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Lachenmeier
authors.forename: Peter
authors.initials: P
authors.lastname: Schmidt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dettmeyer
authors.forename: Burkhard
authors.initials: B
authors.lastname: Madea
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012490:Salsoline Alkaloids / Q000032:analysis / Q000378:metabolism*
chemical_list: D007546:Isoquinolines; D012490:Salsoline Alkaloids; C036617:salsolinol; C020784:norsalsolinol; D004298:Dopamine