Chunk #29 — 2. Neural substrates for the negative emotional state associated with addiction — 2.2. Between-system neuroadaptations that contribute to the negative emotional state component of compulsivity
Brain neurochemical systems involved in arousal-stress modulation also may be engaged within the neurocircuitry of the brain stress systems in an attempt to overcome the chronic presence of the perturbing drug and to restore normal function despite the presence of drug. Both the hypothalamic-pituitary-adrenal axis and the brain stress system mediated by corticotropin-releasing factor (CRF) are dysregulated by chronic administration of all major drugs with dependence or abuse potential, with a common response of elevated adrenocorticotropic hormone, corticosterone, and amygdala CRF during acute withdrawal (Rivier et al., 1984; Merlo-Pich et al., 1995; Koob et al., 1994; Rasmussen et al., 2000; Olive et al., 2002; Delfs et al., 2000). Acute withdrawal from all drugs of abuse also produces an aversive or anxiety-like state that can be reversed by CRF antagonists (see below).
