The glutamate signaling system was broadly affected, with trends similar to those seen in the DRN (McClintick et al., 2015). The overall effect suggests a change in the composition of the glutamate receptors rather than a major reduction in receptor numbers. There are offsetting changes in expression for type I metabotropic receptors (Grm1 and Grm5). Grm1 and Grm5 have downstream effects on phosphoinositide 3-kinase (PI3K). In the PAG, three PI3K associated genes were increased by binge drinking (Pik3c2g, Pik3r2, Pik3r3), along with Akt2. These genes are associated with numerous pathways that were identified by the IPA analysis. Cozzoli et al. (2016) found that male adolescent mice exposed to binge drinking had decreased PI3K activity in the nucleus accumbens; the difference in direction could be related to either brain region or species differences. Among the type III metabotropic receptors (Grm4, Grm7 and Grm8), which are generally pre-synaptic, the increase in the highly expressed Grm4 could offset the decreased expression of Grm7 and Grm8 in terms of total receptor number.
