From use to addiction: receptor loss, hypofrontality, craving and relapse
Explains how chronic use changes the brain: fewer dopamine receptors in the nucleus accumbens, a weakened frontal lobe (hypofrontality), glutamate-driven craving, lost inhibitory control, and relapse.
Where this fitsConnects to 3 · Unlocks 1
- Connects to
- Acute and chronic effects: up- and down-regulation — Dopamine receptor down-regulation is chronic agonism's adaptation.
- Glutamate and GABA: the brain's accelerator and brake — Craving runs through glutamate projections.
- Who becomes addicted: genes, stress and dopamine receptors — Low D2 density appears again — but which came first?
- Unlocks
- Treating addiction: substitution, antagonists, glutamate, vaccines — and the model's limits — Each change suggests a treatment target: receptors, glutamate, relapse.
Orient
From abuse to addiction: reduction of dopamine receptors in the NAc (downregulation) desensitizes the person to natural rewards, with dysphoria and anhedonia when not using. Cortical hypofrontality reduces inhibitory control. Glutamate released onto VTA and NAc sensitizes the reward circuit — cravings. Relapse occurs after abstaining from substance, and then using again.
Course terms
Your professor's wording, word for word from the slides. Learn the term and this definition — the explanation underneath is only there to help it make sense.
- Dopamine receptor downregulation
“Reduction of dopamine receptors in the NAc”Slides 06, p. 7
Downregulation due to persistent drug or DA agonism — “tolerance” to normal rewards.
- Anhedonia
“Dysphoria when not using drugs; anhedonia”Slides 06, p. 7
Anhedonia = inability to feel pleasure from normal rewards.
- Hypofrontality
“Cortical hypofrontality”Slides 06, p. 7
Reduced frontal activity → reduced inhibitory control; occurs after long-term drug use.
- Glutamate and craving
“Glutamate released onto VTA and NAc, sensitizing reward circuit”Slides 06, p. 8
Behaviorally – cravings.
- Relapse
“Relapse occurs after abstaining from substance, and then using again”Slides 06, p. 8
Triggers: re-exposure to drug, conditioned drug cues, stress (including withdrawal).
- Savings
“After relapse, addiction is relearned faster than initially”Slides 06, p. 8
The course calls this “savings on relearning”.
From your course: Course slides 06, pp. 19–23
Tip: the ← and → keys move through the lesson.