Acetyl-coenzyme A (acetyl-CoA) is an intermediate in many biochemical pathways, including those for ethanol metabolism, the citric acid cycle, the mevalonate pathway, and acetylcholine synthesis. One means of acetyl-CoA synthesis is by ligation of acetate and CoA by acetyl-CoA Synthase (AcCoAS). Microarray analysis showed that ethanol exposure transiently and robustly induced expression of AcCoAS by over twofold (Fig. 4A). Flies homozygous for the transposon f03474, inserted in AcCoAS (Fig. 4B), were viable, fertile, and showed no morphological or overt behavioral defects. AcCoAS transcripts were barely detectable in f03474 homozygotes (0.4% ± 0.08% of controls), suggesting that AcCoASf03474 animals may completely lack AcCoAS activity.AcCoASf03474 flies exhibited a marked reduction in Dist (Fig. 4C,D). Reduced hyperactivity was not accompanied by altered ethanol sedation sensitivity (Fig. 4F), and sedated flies recovered fully prior to the second ethanol exposure (not shown). Additionally, AcCoASf03474 flies were able to respond normally to external stimuli as evidenced by the normal magnitude ethanol olfactory startle response in naive animals (mean PS Berlin: 6.1 ± 0.49 mm/s, AcCoASf03474: 6.2 ± 0.49 mm/s, p = 0.823, paired t-test, n =
