Preferred Label : FosB Drug-induction Pathway;
NCIt related terms : FOSB gene expression and drug abuse;
Alternative definition : BIOCARTA: Drug addiction is associated with long-term behavioral changes, suggesting
a long-lived transcriptional regulator that responds to chronic drug exposure might
cause long-term changes in neuronal function. Neurons in the nucleus accumbens and
striatum are involved in addiction and have altered synaptic properties in response
to chronic drug exposure. Along with JunD, delta-FosB is a component of an AP-1 transcription
factor that accumulates in these key brain regions after chronic exposure to drugs
of abuse, including morphine, amphetamine, alcohol, and cocaine. Delta-FosB is an
unusually stable splice variant of the immediate early FosB gene, accumulating and
persisting in the brain long after drug is removed. One component of FosB stability
is post-translational modification through phosphorylation. Genetically modified mice
that selectively overexpress this protein in neurons have increased sensitivity to
cocaine and increased apparent reward response to drug administration, as expected
in addiction, supporting the role of delta-FosB in addiction. The target genes regulated
by delta-FosB include the GluR2 subunit of the AMPA glutamate receptor. Increased
expression of GluR2 modifies the conductance and calcium flux of neurons, and may
be responsible for increased reward responses to drug. Another target of delta-FosB
is the dynorphin gene, the ligand for the kappa opioid receptor, further altering
reward responses to drugs. The cell cycle checkpoint kinase cdk2 is activated by delta-FosB
and acts on Darpp-32 to alter dopaminergic signaling. Although delta-FosB is very
stable, it does degrade after several weeks, while the behavioral changes of drug
addiction persist much longer after drug exposure ends. Changes in chromatin structure
or changes in synaptic structure induced initially by delta-FosB may persist long
after delta-FosB is no longer present, allowing behavioral changes to persist. (This
definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_fosbPathway;
Origin ID : C39083;
UMLS CUI : C1517300;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
