The Brain on Drugs: From Reward to Addiction.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and preclinical concepts without systematic review methodology or primary clinical trial data.
PubMed 26276628 · doi:10.1016/j.cell.2015.07.046
What was done
This is a narrative review synthesizing neuroscience evidence on the circuit- and cellular-level mechanisms underlying the progression from acute drug reward to chronic addiction.
What was found
The abstract provides no quantitative data or specific numerical metrics. It describes how drugs of abuse generate supraphysiologic dopamine surges in the nucleus accumbens, stimulating the direct striatal pathway via D1 receptors while inhibiting the indirect striato-cortical pathway via D2 receptors. Repeated exposure induces neuroplastic alterations in glutamatergic inputs to the striatum and midbrain dopamine neurons, which enhances reactivity to drug cues, diminishes sensitivity to natural non-drug rewards, impairs self-regulation, and elevates sensitivity to stress and dysphoria.
Why it matters
It provides a comprehensive neurobiological framework explaining how chronic substance use co-opts reward, executive function, and affective circuits, defining addiction as a chronic brain disorder with enduring neuroadaptations.
Limits
The abstract describes a broad narrative synthesis without systematic review methodology, meta-analytic pooling, or new empirical human data.
Cited by
- supports Frequent massive dopamine surges lead to desensitization in the nucleus accumbens, requiring higher stimulation to experience pleasure.