To explore the hypothesis that endogenous 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (
salsolinol) might be involved in the etiology of
alcoholism, its concentration was determined in the striatum and adrenal gland of rats bred selectively for disparate alcohol drinking. The alcohol-naive alcohol-preferring (P) and the high-alcohol-drinking (HAD) lines of rats demonstrated significantly lower striatal and adrenal
salsolinol content when compared with the alcohol-non-preferring (NP) and the low-alcohol-drinking (LAD) lines. In the P-line of rats, 4 weeks of free-choice alcohol drinking had no significant effect on striatal
salsolinol levels, although adrenal levels of
salsolinol were significantly higher. The
salsolinol assayed in the striatum of all lines of rats occurred as a racemic mixture of enantiomers that was unchanged following 4 weeks of alcohol exposure. Unlike striatal tissue, the adrenals of alcohol naive P-rats contained significantly more S- than R-
salsolinol (ratio S/R = 83/17) and alcohol consumption resulted in the formation of a nearly racemic mixture of enantiomers. These results suggest a role for genetic factors in the formation of endogenous
salsolinol and its potential regulation by short-term alcohol intake.