In a 2007 collaboration with researchers at the University of Pennsylvania and the University of Colorado at Boulder, Lester postdocs Raad Nashmi and Cheng Xiao and staff biologists Purnima Deshpande and Sheri McKinney created mice with fluorescent a4b2 receptors, and watched the results as the rodents received nicotine doses equivalent to a person smoking two to three packs per day. Over the course of a week or two, the mice sprouted significantly more a4b2 receptors in the midbrain, which processes rewards and is the seat of addiction. (Interestingly, Parkinson’s disease causes some dopamine-producing nerve cells within the midbrain to slowly die off.) When these cells were sprayed with nicotine, they fired about twice as often as cells from “nonsmoking” mice. “We’re essentially taking movies of events inside the neurons during the first minutes, hours, and days of nicotine addiction,” Lester says.
It appears that nicotine acts like a chaperone, a matchmaker, and a traffic cop inside the cell—a combination of roles that maximizes the odds that each nAChR the cell produces will actually reach the cell’s surface. As a chaperone, nicotine binds to nascent receptors’ subunits as they are being synthesized, preventing them from being chewed up by the cell. The details are still being worked out, but “the simple idea is that nicotine stabilizes the receptor in a conformation that does not appeal to the cell's mechanisms for eliminating poorly folded proteins,” says Lester. And, because the receptor’s binding box is made from amino acids on two of the five subunits, nicotine the matchmaker expedites their assembly by binding to the two free-floating halves of the box and holding them in the correct orientation. This gives the remaining three subunits something firm to latch onto, helping them fall into place. And finally, as the cell transports the newly assembled nAChRs to the neuron’s surface, the nicotine molecules bound to the receptors could act like a police escort, once again protecting them from the cell’s protein-digesting machinery.

http://eands.caltech.edu/articles/LX...r_Nicotine.pdf