Given the evidence that neuroimmune signaling contributes to alcohol consumption and dependence (for review see 32), these drugs might be expected to decrease alcohol consumption through their anti-inflammatory effects. However, our data do not support prominent neuroimmune regulation by PPAR agonists. Instead these drugs seem to be targeting neurons and affecting synaptic transmission since there are more genes preferentially expressed in neurons than expected by chance within the PPAR agonist-regulated gene-sets. Moreover, there was a lack of genes associated with microglia in the regulated gene-sets. However, one of the treatment-responsive modules in the amygdala (salmon) was also enriched with microglial, astrocytic and cytokine receptor signaling genes. Overall, the results from WGCNA corroborated the strong neuronal signature of PPAR agonists in the CNS. This neuronal signature was unexpected and represents a surprising and significant finding.
