Question

It is a well-known phenomenon observed in drug addiction, that larger and larger doses of drugs are required over time to get the same effect (or high). Explain why this occurs based on the regulation of receptors the drug binds to and what feedback mechanism is involved.

Answer 1

When a person no longer responds to a drug in the way they did at first, it is known as tolerance. This is the reason why it takes a higher dose of the drug to achieve the same effect compared to when it was first used.
persistent exposure to the drug leads to an adaptive homeostatic response where the drug receptors are down-regulated and the cascade of messages is dampened.
Receptor downregulation is where receptors are inactivated and degraded in response to sustained stimulation.

Receptor deactivation is where the receptor protein gets phosphorylated in response to the excess stimulus (ex. the nicotinic receptor and nicotine).