The dopaminergic mesolimbic pathway in the brain, running from the Ventral Tegmental Area to the Nucleus Accumbens.
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, postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation. Phosphorylated CREB increases levels of ΔFosB, 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 ΔFosB in the neuron. A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated exposure to stimulants through this process. ΔFosB functions as 'one of the master control proteins' that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.