TRYPTOPHAN-PYRROLASE GENE-EXPRESSION IN AN ALCOHOL-PREFERRING AND NONPREFERRING MOUSE STRAIN

There is considerable evidence that the level of cerebral serotonin pl ays a key role in the volitional consumption of ethanol in both man an d animals. Naive alcohol-preferring C57BL/6J mice have been shown to h ave a lower cerebral serotonin content compared to the non-preferring CBA/Ca mouse strain. This has been attributed to the enhancement of he patic tryptophan pyrrolase activity in C57 mice. Activity and/or expre ssion of tryptophan pyrrolase may be an important biological determina nt of alcohol preference. We have investigated the possible mechanism/ s underlying this strain difference in tryptophan pyrrolase activity b y assaying both mRNA levels encoding for the tryptophan pyrrolase gene and by mutational analysis of tryptophan pyrrolase cDNA. We were unab le to demonstrate any difference in tryptophan pyrrolase mRNA levels b etween naive C57 and CBA mice. Tryptophan pyrrolase mRNA levels were i ncreased following starvation in C57 mice and following glucocorticoid administration in both C57 and CBA mice. Heteroduplex mutational anal ysis failed to detect any tryptophan pyrrolase cDNA sequence heterogen eity between these mice strains.