Why smoking is so terribly addictive

Researchers have tried to explain how nicotine exploits the body’s cellular machinery to promote addiction.

According to the Center for Disease Control and Prevention, nicotine activates receptors known as nAChRs and, remarkably, unlike most other drugs of abuse, it acts as a “pharmacological chaperone” to stabilize assembly of its receptors within the Endoplasmic Reticulum (ER) and increase their abundance at the cell surface (up-regulation).

Up-regulation of nAChRs plays a major role in nicotine addiction and, possibly, in the decreased susceptibility of smokers to Parkinson’s disease.

Receptors containing an alpha6 subunit (alpha6* nAChRs) are abundant in several specific brain regions.

Researchers from the California Institute of Technology in Pasadena used mice expressing alpha6 labeled with a fluorescent protein to show that exposure to nicotine—at a level comparable to that in human smokers—up-regulated alpha6* nAChRs in these areas of the brain.

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