FOSB

FBJ murine osteosarcoma viral oncogene homolog B also known as FOSB (in humans) or FosB (in other species) is a protein that, in humans, is encoded by the FOSB gene.

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
Delta FosB is a truncated splice variant of FosB. Delta FosB has been implicated in the development of drug addiction and control of the reward system in the brain, and is linked to changes in a number of other gene products such as CREB and sirtuins. Delta FosB also regulates the commitment of mesenchymal precursor cells to the adipocyte or osteoblast lineage.

Role in cocaine use
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.