With repeated exposure to drugs of abuse or to stress, isoforms of ΔFosB accumulate due to their very high level of stability and eventually become the predominant Fos-like protein in these neurons. This phenomenon is observed in response to chronic administration of virtually any drug of abuse. It is also observed after high levels of consumption of natural rewards (exercise, sucrose, high fat diet, sex). As well, it is observed in response to several types of chronic stress. However, different neuronal cell types are involved: drugs and natural rewards induce ΔFosB in a single subtype of nucleus accumbens neuron, while stress induces the protein more broadly in this brain region.
These ΔFosB responses are interesting because they provide a molecular mechanism (based in the stability of the protein) by which drugs of abuse, natural rewards, and stress can induce long-lasting changes in gene expression.
What is the nucleus accumbens?
The nucleus accumbens definitely plays a central role in the reward circuit. Its operation is based chiefly on two essential neurotransmitters: dopamine, which promotes desire, and serotonin, whose effects include satiety and inhibition. Many animal studies have shown that all drugs increase the production of dopamine in the nucleus accumbens, while reducing that of serotonin.
The locus coeruleus, an alarm centre of the brain and packed with norepinephrine, is another brain structure that plays an important role in drug addiction. When stimulated by a lack of the drug in question, the locus coeruleus drives the addict to do anything necessary to obtain a fix.
You know all those spree killings associated with antipsychotics?
ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes
Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis
Transcriptional mechanisms of addiction: role of ΔFosB
ΔFosB: A sustained molecular switch for addiction
The Influence of ΔFosB in the Nucleus Accumbens on Natural Reward-Related Behavior
Regulation of ΔFosB Stability by Phosphorylation