Dopamine, addiction and reward

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Abstract

The role of dopamine was inferred in reward processes from early studies showing that psychomotor stimulants such as cocaine and amphetamine could facilitate intracranial self-stimulation. Subsequent studies showed that dopamine-receptor antagonists could attenuate brain stimulation reward and completely block the reinforcing effects of cocaine and amphetamine as measured by direct intravenous self-administration of these drugs. A specific dopaminergic substrate for both the facilitation of brain stimulation reward and the self-administration of psychomotor stimulants appears to be the region of the nucleus accumbens in the forebrain. This structure receives significant limbic afferents and has significant projections to the extrapyramidal motor system. Chronic administration of cocaine and amphetamine seem to have the opposite effects to acute injections and during withdrawal lead to increases in brain stimulation reward thresholds and decreases in dopamine release in the nucleus accumbens. This same nucleus accumbens dopamine projection seems to be critical for the motor activation associated with the anticipation of both drug and non-drug rewards. These results suggest that drugs that activate the mesolimbic dopamine system have such powerful reinforcing effects because they facilitate the attentional-motor systems critical for approach behaviour and the behavioural activation associated with incentive-motivation.

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