Protein fosB, also known as FosB and G0/G1 switch regulatory protein 3 (G0S3), is a protein that in humans is encoded by the FBJ murine osteosarcoma viral oncogene homolog B (FOSB) gene.
Gene location Chromosome 19
The FOS gene family consists of four members: FOS, FOSB, FOSL1, and FOSL2.
These genes encode proteins that can dimerize with proteins.
FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation.
FosB and its truncated splice variants, FosB, are involved in osteosclerosis.
The FosB splice variant has a central, role in the development and maintenance of addiction.
FosB overexpression produces a pronounced gene-related phenotype
that triggers the development of addiction-related neuroplasticity throughout the reward system and produces a behavior characteristic of an addiction.
DeltaFosB is a truncated splice variant of the FOSB gene.
FosB is a critical factor in the development of all forms of behavioral and drug addictions.
FosB is linked to changes in the brain’s reward system, with in a number of other Proteins.
FosB in the brain’s nucleus accumbens, functions as a molecular switch and a control protein in the development of an addiction.
FosB regulates the commitment of mesenchymal precursor cells to the adipocyte or osteoblast lineage.
FosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.
FosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.
FosB is the key transcription factor involved in addictions to natural rewards.
Activated or overexpressed FosB precipitates a series of transcription events that produces an addictive state: that is compulsive reward-seeking behavior involving a particular stimulus.
Activated or overexpressedFosB triggers a series of transcription events that ultimately produce an addictive state.
It is sustained for months after cessation of drug use due to the abnormal and exceptionally long half-life of FosB isoforms.
FosB is identified with compulsive sexual activity as an addiction.
There is a reward cross-sensitization between amphetamine and sexual activity, meaning that exposure to one increases the desire for both, and is clinically as a dopamine dysregulation syndrome.
FosB expression is required for this cross-sensitization effect, which intensifies with the level of FosB expression.
FosB expression in nucleus accumbens medium spiny neurons regulates drug self-administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion.
Addiction arises through the overexpression of DeltaFosB (ΔFosB), a transcription factor, in the D1-type medium spiny neurons of the ventral striatum.
ΔFosB is an inducible gene which is increasingly expressed in the nucleus accumbens as a result of repeatedly overdosing on an addictive drug or overexposure to other addictive stimuli.
FosB expression is addiction biomarker and that the degree of accumbal FosB induction by a drug is a metric for how addictive it is relative to others.
The signaling cascade in the nucleus accumbens results in psychostimulant addiction.
The signaling events in the brain’s reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine.
Following presynaptic dopamine and glutamate co-release by such psychostimulants, postsynaptic receptors for these neurotransmitters trigger internal signaling events.
These signaling events act through a cAMP-dependent pathway and a calcium-dependent pathway that ultimately result in increased CREB phosphorylation.
CREB phosphorylated increased levels of deltaFosB, which in turn represses the c-Fos gene with the help of corepressors.
c-Fos repression acts as a molecular switch that enables the accumulation of DeltaFosB in the neuron.
A phosphorylated form of DeltaFosB persists in neurons for 1-2 months, slowly accumulates following repeated high-dose exposure to stimulants.
DeltaFosB functions to produce addiction-related structural changes in the brain, and upon sufficient accumulation induces an addictive state.
Chronic addictive drug use causes alterations in gene expression in the mesocorticolimbic projection of the brain.
These gene expression changes arise through transcriptional and epigenetic mechanisms.
The most important transcription factors that produce these alterations are: DeltaFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NF-KB).
FosB is the most significant biomolecular mechanism in addiction because the overexpression of
deltaFosB in the D1-type medium spiny neurons in the nucleus accumbens.
FosB is necessary for many of the neural adaptations and behavioral effects as increases in drug self-administration and reward sensitization, seen in drug addiction.
FosB overexpression implicated in addictions to: alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and amphetamines,
FosB is inhibited and its function is opposed the function of JunD, a transcription factor, and G9a, a histone methyltransferase.
Increases in nucleus accumbens JunD expression or G9a expression can even block, many of the neural and behavioral alterations seen in chronic drug abuse.
FosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.
Natural rewards, drugs of abuse induce gene expression of DeltaFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through DeltaFosB overexpression.
FosB is the key mechanism involved in addictions to natural rewards and behavioral addictions as well.
FosB is the most significant biomolecular mechanism in addiction.
Overexpression of DeltaFosB in the nucleus accumbens is a necessary common for all known forms of addiction.
FosB is a strong positive modulator of positively reinforced behaviors.
The overexpression of DeltaFosB in the medium spiny neurons in the nucleus accumbens causes neural adaptations and behavioral effects of increases in drug self-administration and reward sensitization seen in drug addiction, while decreasing sensitivity to aversion
DeltaFosB in the nucleus accumbens of the brain reinforced effects of sexual reward.
Dopaminergic psychostimulants, such as amphetamine and sexual behavior have similar biomolecular mechanisms to induce FosB in the nucleus accumbens and possess bidirectional reward effects mediated through FosB.
This explains the dopamine dysregulation syndrome, characterized by drug-induced compulsive engagement in natural rewards: sexual activity, shopping, and gambling observed in some individuals taking dopaminergic medications.
FosB inhibitors, that oppose its action or reduce its expression may be an effective treatment for addiction and addictive disorders.
FosB levels increase upon the use of cocaine.
Elevated levels of FosB increases in brain-derived neurotrophic factor (BDNF) levels, which in turn increases the number of dendritic branches and spines present on neurons involved with the nucleus accumbens and prefrontal cortex areas of the brain.
FosB expression in the nucleus accumbens increases resilience to stress.
FosB expression is induced in the nucleus accumbens region by acute exposure to social defeat stress.
Antipsychotic drugs have been shown to increase DeltaFosB.
Altered dopamine neurotransmission is frequently observed in the nucleus accumbens following the development of an addictive state.