Drug addiction has afflicted mankind for centuries, yet the mechanisms by which particular
drugs lead to addiction, and the genetic factors that make some individuals particularly
vulnerable to addiction, have remained elusive. From a clinical perspective, drug abuse
continues to exact enormous human and financial costs on society, yet all currently available
treatments for drug addiction are notoriously ineffective. The search for a better
understanding of the neurobiological mechanisms underlying the addictive actions of drugs …

Regulation of gene expression is one mechanism by which drugs of abuse can induce
relatively long-lasting changes in the brain to cause a state of addiction. Here, we focus on
two transcription factors, CREB (cAMP response element binding protein) and ΔFosB, which
contribute to drug-induced changes in gene expression. Both are activated in the nucleus
accumbens, a major brain reward region, but mediate different aspects of the addicted state.
CREB mediates a form of tolerance and dependence, which dampens an individual's …