Chunk #24 — 2. Neural substrates for the negative emotional state associated with addiction — 2.1. Within-system neuroadaptations that contribute to the negative emotional state component of compulsivity
Electrical brain stimulation reward or intracranial self-stimulation has a long history as a measure of activity of the brain reward system and of the acute reinforcing effects of drugs of abuse. All drugs of abuse, when administered acutely, decrease brain stimulation reward thresholds (Kornetsky and Esposito, 1979) and when administered chronically increase reward thresholds during withdrawal (see above). Brain stimulation reward involves widespread neurocircuitry in the brain, but the most sensitive sites defined by the lowest thresholds involve the trajectory of the medial forebrain bundle that connects the ventral tegmental area with the basal forebrain (Olds and Milner, 1954; Koob et al., 1977). While much emphasis was focused initially on the role of the ascending monoamine systems in the medial forebrain bundle, other nondopaminergic systems in the medial forebrain bundle clearly have a key role (Hernandez et al., 2006).
