Answer: DeltaFosB is a protein that is upregulated in addiction.
When a person is addicted to a drug, their brain undergoes a variety of changes that makes it very difficult for them to stop drug use. They become obsessed with obtaining and using the drug, many times to the detriment of their personal lives or obligations. The idea that there are permanent neurological changes in the brain that lead to addiction is described as the brain disease model of addiction (BDMA).
The BDMA centers around the "reward circuitry" of the brain, structures such as the ventral tegmental area (VTA) of the midbrain and the nucleus accumbens (NAcc) of the basal forebrain. This pathway uses dopamine as the main neurotransmitter signal. Dopamine synthesized by the cells in the VTA is released into the NAcc, where it can then activates dopamine receptors expressed on neurons in the NAcc. This release is increased when an animal is exposed to something particularly salient in their environment. We usually think of this dopamine release signal as increasing when a positive, unexpected outcome is experienced, including naturally rewarding stimuli like food or water.
According to the brain disease model of addiction, this dopamine release system is permanently changed after long-term exposure to drugs of abuse. These changes are multifaceted, but one potential marker of the neural changes that accompany compulsive drug use and behavioral addictions is a protein called deltaFosB. When deltaFosB is upregulated, rodents experience addiction-like characteristics, such as being willing to self-administer cocaine at low doses and to work harder for drug access in a progressive ratio test. (ΔFosB: A sustained molecular switch for addiction)
On a molecular scale, deltaFosB is a transcriptional regulator. When levels are elevated, other proteins such as CREB or Cdk5 also increase their expression. The leading argument in favor of deltaFosB as being important for drug abuse is that the up regulation of the protein is elevated for months after discontinuation from drug exposure.
One of the main links between deltaFosB and drug abuse has been demonstrated with the psychostimulant cocaine. Repeated dosings with cocaine increases levels of deltaFosB in the nucleus accumbens, an important site of action of the dopamine reward pathway. (Cocaine and the AP-1 transcription factor complex.) The result of increased deltaFosB is related to a similar increase in a signaling molecule called brain derived neurotrophic factor, or BDNF. BDNF works at the level of the dendrites to induce plasticity, inducing a physical structural change that results in altered signaling in response to future incoming stimuli.
Many other drugs of abuse change deltaFosB levels in critical limbic pathways. For example, nicotine increases deltaFosB in the amygdala (Nicotine-induced CREB and DeltaFosB activity is modified by caffeine in the brain reward system of the rat). Ethanol, the psychoactive component of alcohol, also upregulates deltaFosB expression (Region-specific induction of FosB/ΔFosB by voluntary alcohol intake: effects of naltrexone). Notably, opioid drugs such as morphine also increase deltaFosB (An essential role for DeltaFosB in the nucleus accumbens in morphine action), demonstrating the importance of this protein as serving a function in a variety of addictive processes.