Another example is provided by the transcriptional effects of long-term free-choice ethanol drinking. A recent study took advantage of the inherent inter-individual variability in the ethanol intake of inbred C57Bl/6N mice to explore the “non-genetic” determinants of ethanol drinking [29]. Mice were subjected to four cycles of four 18-h two-bottle choice (10% w/v ethanol/water) drinking sessions, followed by four days of ethanol deprivation, and sacrificed 6 days after the last drinking session. Genes whose expression level correlated with stabilized ethanol intake (889 in nucleus accumbens, 850 in prefrontal cortex and 559 in ventral midbrain) were associated with glutamate signaling, brain-derived neurotrophic factor (BDNF) signaling, synaptic vesicle function and epigenetic modifications. In the nucleus accumbens, there was a striking enrichment for genes involved in transcriptional repression through epigenetic modifications (histone deacetylation and DNA methylation), and in synaptic vesicle formation and recycling. In the prefrontal cortex, mitochondrial dysfunction and glutamate signaling were highlighted, while functional categories over-represented in the ventral midbrain suggested that cell migration may be affected.
