Repeated challenges, such as with drugs of abuse, lead to attempts of the brain via molecular, cellular, and neurocircuitry changes to maintain stability but at a cost. For the drug addiction framework elaborated here, the residual deviation from normal brain reward threshold regulation is termed an allostatic state. This state represents a combination of chronic elevation of reward set point fueled by decreased function of reward circuits and recruitment of anti-reward systems, both of which lead to the compulsivity of drug-seeking and drug-taking. How these systems are modulated by other known brain emotional systems localized to the basal forebrain, where the ventral striatum and extended amygdala project to convey emotional valence, how the dysregulation of brain emotional systems impact on the cognitive domain linked to impairments in executive function, and how individuals differ at the molecular-genetic level of analysis to convey loading on these circuits remain challenges for future research.
