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.
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