acts as a co-agonist for NMDA signaling (Oliet and Mothet, 2009). Any or all of these roles for serine may be affected by increased serine synthesis following ethanol exposure. Alterations in membrane lipid physiology correlate with resistance to lethal ethanol concentrations in flies (Montooth et al., 2006), and phospholipid synthesis and signaling pathway changes are induced by ethanol consumption in the mammalian liver (Baraona and Lieber, 1979). In flies, the fat bodies perform many functions of the mammalian liver and thus may be the site of serine regulation by ethanol. The role of the fat bodies in ethanol behavioral responses is not known. While a role for d-serine has yet to be uncovered in flies, the presence of the enzyme serine racemase indicates that it can be synthesized from l-serine, and up-regulation of serine racemase expression by ethanol suggests that ethanol exposure results in increased d-serine availability. Moreover, glutamatergic NMDA receptor signaling is a major target of ethanol in mammals at concentrations similar to those used for our microarray study (Lovinger et al., 1989). It will be important to determine the mechanisms by which the regulation of serine synthesis contributes to the effects of ethanol.
