CHRONIC ETHANOL INHIBITS INOSITOL METABOLISM IN SPECIFIC BRAIN-REGIONS

Many neurotransmitters and hormones in the nervous system transmit sig nals through receptors coupled to the poly-phosphoinositide (PI) signa ling pathway. In this study, an in vivo protocol with [H-3]inositol wa s used to examine the effect of chronic ethanol administration on inos itol metabolism and posy-PI turnover in the cerebral cortex, hippocamp us, and cerebellum of mouse brain. C57BL/6 mice were given a nutrition ally complete liquid diet containing either ethanol (5%, w/v) or isoca loric sucrose for 2 months. Mice were injected intracerebrally with [H -3]inositol; after 16 or 24 hr, they were injected intraperitoneally w ith lithium (8 mEq/kg body weight) to inhibit the inositol monophospha tase (IP1) activity. All mice were decapitated 4 hr after lithium inje ction. Labeled inositol phospholipids accounted far 16 to 23% of total labeled inositol in different regions of control mouse brain, and the percentages in the hippocampus were consistently higher than the cere bral cortex and cerebellum. In control mice, the percentages of labele d IP1 after a 4-hr lithium treatment were 11.5%, 9.9%, and 3.7% for ce rebral cortex, hippocampus, and cerebellum, respectively. Chronic etha nol feeding resulted in a significant (p < 0.05) decrease in the perce nt of labeled IP1 and inositol phospholipids, and this effect was obse rved in the cerebral cortex and, to a lesser extent, hippocampus but n ot cerebellum. When ratios of labeled IP1 were expressed against label ed inositol phospholipids as an index of the poly-PI turnover activity , significant decreases in IP/lipid ratios were observed in the cerebr al cortex, but not the hippocampus or cerebellum. Although mice killed 24 + 4 hr after the last ethanol feeding would have experienced an 8- hr period of ethanol withdrawal, compared with the 16 + 4-hr group, no differences in IP/lipid ratios were observed between the two time gro ups. These results illustrate regional differences in the effect of ch ronic ethanol on inositol metabolism. In the brain, but no difference in poly-PI turnover in brain due to ethanol withdrawal.