In animal studies, upregulation of ΔFosB, a product of the Fosb gene induced by chronic administration of virtually all drugs of abuse was found to persists for several weeks and may maintain stable expression of genes associated with drug addiction [73], [74]. Dysregulation of the NF-κB system observed in the present study is associated with chronic alcoholism, and as such represents the first example of sustained transcriptional adaptation to chronic intake of substances of abuse in the human brain. The sustained adaptations in the NF-κB system apparently represent a shift to new steady state or allostatic levels in the NF-κB/p50 activities that may underlie persistent alterations in expression of their target genes. Multiple mechanisms may ensure the stability of alterations that, hypothetically, may involve a) the feedback loop between NF-κB and IκB [75]; b) feed-back and feed-forward NF-κB/p50 interactions with other transcription factors such as DAXX [58], glucocorticoid receptors [76], SP-1 [77] and CREB [29].
