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.
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- 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?
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- Treating addiction: substitution, antagonists, glutamate, vaccines — and the model's limits — Each change suggests a treatment target: receptors, glutamate, relapse.
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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.
Términos del curso
Las palabras de tu profesor, tal cual aparecen en las diapositivas. Aprende el término y esta definición; la explicación de abajo solo ayuda a entenderla.
- Dopamine receptor downregulation
“Reduction of dopamine receptors in the NAc”Diapositivas 06, p. 7
Downregulation due to persistent drug or DA agonism — “tolerance” to normal rewards.
- Anhedonia
“Dysphoria when not using drugs; anhedonia”Diapositivas 06, p. 7
Anhedonia = inability to feel pleasure from normal rewards.
- Hypofrontality
“Cortical hypofrontality”Diapositivas 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”Diapositivas 06, p. 8
Behaviorally – cravings.
- Relapse
“Relapse occurs after abstaining from substance, and then using again”Diapositivas 06, p. 8
Triggers: re-exposure to drug, conditioned drug cues, stress (including withdrawal).
- Savings
“After relapse, addiction is relearned faster than initially”Diapositivas 06, p. 8
The course calls this “savings on relearning”.
De tu curso: Course slides 06, pp. 19–23
Consejo: las teclas ← y → recorren la lección.