Addiction
![Signaling cascade in the nucleus accumbens that results in psychostimulant addiction
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Nuclear pore
Nuclear membrane
Plasma membrane
Cav1.2
NMDAR
AMPAR
DRD1
DRD5
DRD2
DRD3
DRD4
Gs
Gi/o
cAMP
cAMP
PKA
CaM
CaMKII
DARPP-32
PP1
PP2B
CREB
ΔFosB
JunD
c-Fos
SIRT1
HDAC1
[Color legend 1]
This diagram depicts 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,[35][36] postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation.[37][38][39] Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fos gene with the help of corepressors;[38] c-Fos repression acts as a molecular switch that enables the accumulation of ΔFosB in the neuron.[40] A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated high-dose exposure to stimulants through this process.[41][42] ΔFosB functions as](/uploads/202501/30/ΔFosB.svg3441.png)
![Top: this depicts the acute expression of various Fos family proteins following an initial exposure to an addictive drug.Bottom: this illustrates increasing ΔFosB expression from repeated twice daily drug binges, where these phosphorylated (35–37 kD) ΔFosB isoforms persist in mesolimbic dopamine neurons for up to 2 months.[52][42]](/uploads/202501/30/ΔFosB_accumulation.svg3441.png)
Addiction is a medical condition that is characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. It can be thought of as a disease or biological process leading to such behaviors. The two properties that characterize all addictive stimuli are that they are reinforcing (i.e., they increase the likelihood that a person will seek repeated exposure to them) and intrinsically rewarding (i.e., something perceived as being positive or desirable).