Ethanol driven gene expression in TAP and TAR rat brains

Taste aversion (TA) prone and TA resistant (TAR) rat lines have been bred to facilitate studies of TA conditionability. Between line differences in TA conditionability are maintained when an injection of ethanol is substituted for cyclophosphamide, the emetic-class agent used for line selection. TAR rats also self-administer much more ethanol and attain higher blood alcohol concentrations than TAP rats. Thus, genetically mediated differences in aversive aftereffects of alcohol may contribute to alcoholism risk potential. Consistent with clinical and preclinical literature, TAR rats have lower serotonin (5-HT) brain levels and less efficient 5-HT transport than alcohol adverse TAR rats. However, polygenetic control is likely and other systems merit study. An oligonucleotide probe array representing more than 1200 neuroscience relevant genes was used to measure TAP/ TAR expression differences in the amygdala 6 hours after an ip 1.25g/kg ethanol injection. Eighteen expression differences of 2-fold or greater (range = 88.5 to 2) were detected in the GABA, 5-HT, acetylcholine, and glutamate/aspartate systems. The results advance candidate genes to be targeted within molecular biological analyses of alcohol dependency risk factors and during attempts to develop new pharmacotherapies.