The Brain Stress System in the Neurobiology of the “Dark Side” of Addiction and Its Relation to Neurodegeneration

Addiction is a chronically relapsing disorder characterized by a compulsion to seek and take a substance of abuse, the development of dependence, and a negative emotional state when intake is stopped. Compelling evidence argues that dysregulation of the brain stress system is a key constituent of the addiction process. Through mechanisms of negative reinforcement, the stress system is posited to induce negative emotional state referred to as the ‘dark side of addiction’ as it becomes the powerful motivation for drug-seeking associated with compulsive use. Therein, the neuropharmacological actions of corticotropin-releasing factor (CRF) is posited to play a key role in the anxiety/stress-like effects of acute withdrawal, anxiety/stress-like effects of abstinence, and relapse to drug taking. In this view, the present chapter sheds a critical light on latest research developments implicating this largely neglected component of substance abuse to give insight into the neuropathology of the ‘dark side’ of addiction. Moreover, the chapter provides insight into individual vulnerability to addiction and proposes a novel treatment candidate for the disorder.