Making sense of addiction

Marina Picciotto, Ph.D., says that while she was growing up in Manhattan, she was “one of those scattered people who did well in school but got yelled at by the teachers.” In science labs, however, “that was never a problem.” At the magnet high school she attended, students completed graduation requirements early, and took on full-time internships as seniors. Somewhat by chance, she came across an opening in a lab at the Rockefeller University, where she worked on studies of feeding behavior in rats that would neatly foreshadow her later career.

After earning a B.S. in biology at Stanford University, Picciotto returned to Rockefeller as a Ph.D. student in molecular neuroscience. Her mentor there was Paul Greengard, Ph.D., who would later receive the Nobel Prize for his work—a great deal of which he had accomplished while on the Yale School of Medicine faculty—explaining the molecular basis of communication among nerve cells in the brain.

In Greengard’s lab, Picciotto studied signal transduction and the transport of ions across nerve cell membranes. “It was very satisfying, because you could actually say, ‘this goes with this’ [and make] pictures that made sense. But I was always sneakily trying to get back to [the question], What do those molecules mean for complex behaviors?”

It’s a question that has driven Picciotto’s research ever since. As a postdoctoral fellow at the Institut Pasteur in Paris, France, she began studying nicotinic acetylcholine receptors (nAChRs), proteins in nerve cells that are activated by the neurotransmitter acetylcholine, but also respond to chemicals like nicotine. She describes this research the way many describe their first cigarette: “Once I started, I was hooked.”

In 1995 she joined the School of Medicine’s faculty as an assistant professor. Now the Charles B.G. Murphy Professor of Psychiatry and professor of neurobiology and pharmacology, Picciotto studies the links between neurochemical signaling and behavior. Her primary interest is the role of nAChRs in brain development and function, with a special emphasis on behaviors related to nicotine addiction and smoking.

“What’s really cool about investigating nicotinic acetylcholine receptors is what happens when you stimulate them,” Picciotto says. For instance, in 2011, she and lab member Yann S. Mineur, Ph.D., associate research scientist, teamed up with colleagues in the Section of Comparative Medicine to show that a specific type of nicotinic receptor is the crucial trigger for nicotine’s effects on appetite suppression and weight-loss in mice. The study, published in Science, could lead to new strategies to treat obesity.

Picciotto also studies galanin, a neuropeptide that works to modulate acetylcholine but also heightens the effects of opiate drugs—many of which are addictive. In 2003, she published research in Proceedings of the National Academy of Sciences showing that in addition to increasing the pain-fighting effects of opiates, galanin also decreased their addictive properties. Her lab continues to explore how manipulating galanin might combat addiction and withdrawal symptoms.

“We’re never going to understand all the molecules necessary for an entire behavior,” Picciotto says, “but the overall philosophy—that you can say something meaningful about molecules in the brain that can inform how we think about the molecular basis of behavior—that’s something that’s approachable, and it’s worth doing.”