Alcohol induces formation of morphine precursors in the striatum of rats.
Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to play a role in the pathogenesis of alcoholism. The present study describes the alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and Norcoclaurine in the rat brain. These compounds are of special interest since both were found as being intermediates in the biosynthesis of morphine in the opium poppy. The concentration of both TIQs were determined in different brain regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas chromatography/mass spectrometry was used for the detection and quantification of the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in the striatum of those rats which had consumed alcohol for 18 month, neither in other brain regions nor in any brain regions of the controls or the short term (6 month) alcohol treated rats. These findings and the fact that those tetrahydroisoquinolines were only detected in the striatum of the alcohol fed rats and were present only as the S-enantiomers suggest that an alcohol induced biosynthetic pathway exists in the mammalian brain.
Haber
H
H
Research Institute of Molecular Pharmacology, Berlin, Germany. Haber@fmp.fta-berlin.de
Roske
I
I
Rottmann
M
M
Georgi
M
M
Melzig
M F
MF
D000470:Alkaloids / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D009022:Morphine Derivatives / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines; D013765:Tetrahydropapaveroline / Q000378:metabolism
D000470:Alkaloids; D009022:Morphine Derivatives; D044005:Tetrahydroisoquinolines; D000431:Ethanol; D013765:Tetrahydropapaveroline; C012348:higenamine