The major findings of this study are that multiple scheduled (4 × 1 hour sessions during the dark cycle) sessions of concurrent access to 10, 20 and 30% ethanol a) resulted in ‘loss-of-control’ alcohol drinking (Fig. 1), defined as drinking that routinely produces BECs exceeding 200 mg%, and b) produced major changes (mainly 1.2-fold and higher in 211 unique genes) in expression of genes in the VTA (Table 1). Genes that are involved in transcription, metabolic processes, cell-to-cell interactions, inflammatory response, and response to hormone stimuli were particularly affected (Tables 7 and 8). The overall results support the idea that this level of drinking is producing major changes in gene expression within the VTA that could promote neuroadaptations mediating excessive alcohol drinking and alcohol-induced neuronal damage.