INSTRUCTION: Read the following text to answer the question.

When nicotine enters the lungs, it’s in the brain 20 seconds later. In this journey, nicotine has traveled through the cells in the lungs to the blood — and then from the blood to the brain, passing through the blood‑brain barrier. In all, nicotine passes through six membranes when it’s smoked or vaped.

Once nicotine is in the brain, it activates the most sensitive nicotinic receptors on membranes of nerve cells, or neurons, but it also travels through the membrane to enter the neuron. Finally, it passes into the organelles of the neuron, where proteins, including the nicotinic receptor, are being made. When a person smokes, nicotine actually helps the cell to assemble more nicotinic receptors, which travel out of the endoplasmic reticulum (part of the cellular transportation system) and onto the surface of the cell. It’s as though nicotine is acting as a pharmacological “chaperone” to bring those receptors to the surface of the cell.

We have labeled this process “inside out” pharmacology. In trying to unravel the cell biology of nicotine addiction, my lab and others study how this so‑called chaperoning or upregulating of nicotinic receptors is necessary for the early stages of nicotine dependence, ultimately underlying the brain’s addiction to nicotine. When a person stops taking nicotine, the natural acetylcholine cannot sufficiently activate the upregulated receptors. They produce craving and other symptoms of withdrawal.