Acute and chronic effects: up- and down-regulation
Explains why a drug's effect changes with repeated use: receptors turn down when overstimulated and turn up when blocked. This is cellular-adaptive tolerance — and the source of rebound and withdrawal.
Where this fitsConnects to 2 · Unlocks 2
- Connects to
- Therapeutic window, steady state, washout — and tolerance — Adds the pharmacodynamic kind of tolerance to the metabolic kind from pharmacokinetics.
- Plasticity and neurogenesis — Receptor regulation is one form of the brain's plasticity.
- Unlocks
- Substance use disorder: dependence is not addiction — Physical dependence is exactly these adaptations — which is why dependence isn't the same as addiction.
- From use to addiction: receptor loss, hypofrontality, craving and relapse — Dopamine receptor down-regulation in addiction is this process in the reward circuit.
Orient
When a drug binds to a receptor it produces an acute response (behavioral drug effects). When the drug is given over a longer period it produces chronic changes in the properties of the receptors: down-regulation (desensitization) after increased activity, and up-regulation (supersensitization) after decreased activity — the basis of cellular adaptive tolerance.
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.
- Acute response
“When a drug binds to a receptor it produces an acute response (behavioral drug effects)”Slides 05, p. 8
The immediate effect of a dose.
- Down-regulation
“Down-regulation (desensitization) after increased activity”Slides 05, p. 8
Chronic agonist use → fewer or less responsive receptors → tolerance; stopping abruptly → rebound (e.g., rebound anxiety).
- Up-regulation
“Up-regulation (supersensitization) after decreased activity”Slides 05, p. 8
Chronic antagonist use → more responsive receptors; stopping abruptly → rebound (e.g., rebound psychosis).
- Cellular adaptive tolerance
“Basis of cellular adaptive tolerance”Slides 05, p. 8
One of three tolerances, with metabolic and behavioral.
From your course: Course slides 05, pp. 8–9, 13 · Course slides 04, p. 50
Tip: the ← and → keys move through the lesson.