FBJ murine osteosarcoma viral oncogene homolog B also known as FOSB or FosB is a protein that, in humans, is encoded by the FOSBgene.
The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation.
Delta FosB levels have been found to increase upon the use of cocaine. Each subsequent dose of cocaine will continue to increase the levels of Delta FosB with no ceiling of tolerance. Increasing the levels of Delta FosB has led to increases in brain-derived neurotrophic factor (BDNF) levels, which in turn will increase the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug. This consequence of cocaine use may attribute to the idea of sensitization presented with the drug.
Transgenic mice exhibiting inducible expression of delta FosB primarily in the nucleus accumbens and dorsal striatum exhibit sensitized behavioural responses to drugs. They self-administer cocaine at lower doses than control, but have a greater likelihood of relapse when the drug is withheld. Delta FosB increases the expression of AMPA receptor subunit GluR2 and also decreases expression of dynorphin, thereby enhancing the sensitivity to reward.
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^ abcdefghijNestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clin Psychopharmacol Neurosci10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMC3569166. PMID23430970. "ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states."
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