Chunk #25 — 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
Within-system neuroadaptations to chronic drug exposure include decreases in function of the same neurotransmitter systems in the same neurocircuits implicated in the acute reinforcing effects of drugs of abuse. One prominent hypothesis is that dopamine systems are compromised in crucial phases of the addiction cycle, such as withdrawal and leads to decreased motivation for non-drug-related stimuli and increased sensitivity to the abused drug (Melis et al., 2005). Activation of the mesolimbic dopamine system has long been known to be critical for the acute rewarding properties of psychostimulant drugs and to be associated with the acute reinforcing effects of other drugs of abuse (Koob, 1992; Di Chiara and North, 1992; Nestler, 2005). Decreases in activity of the mesolimbic dopamine system and decreases in serotonergic neurotransmission in the nucleus accumbens occur during drug withdrawal in animal studies (Rossetti et al., 1992; Weiss et al., 1992, 1996). Imaging studies in drug-addicted humans have consistently shown long-lasting decreases in the numbers of dopamine D2 receptors in drug abusers compared with controls (Volkow et al., 2002). In addition, cocaine abusers have reduced dopamine release in
