Nicotine Causes Selective Degeneration In Brain, UCLA Neuroscientists Report

"Nicotine causes the most selective degeneration in the brain that I have ever seen," said UCLA neuroscientist Gaylord Ellison, a professor of psychology and member of UCLA's Brain Research Institute. "Only one tract of the brain is affected."

The part of the brain that is affected by nicotine is called fasciculus retroflexus, which has two halves. In previous research conducted over more than two decades, Ellison's research team has shown that such drugs as amphetamines, cocaine and ecstasy damage one half of fasciculus retroflexus. In the journal Neuropharmacology and at the Society for Neuroscience's annual meeting in New Orleans this month, Ellison's research team reports for the first time that nicotine causes degeneration in the other half of fasciculus retroflexus. The neuroscientists further report that the drugs that damage one half of fasciculus retroflexus do not damage the other half that nicotine affects.

"Our findings suggest that this (fasciculus retroflexus) is the brain's weak link for stimulant addictive drugs," Ellison said. "This tract is affected more by chronic drug use than any other tract in the brain.

"It seems likely that fasciculus retroflexus is linked to drug addiction and relapse," Ellison said. "In chronic smokers, this tract may well play a major role in the addiction to nicotine."

Fasciculus retroflexus is a pathway that emerges from the brain's habenula, which is above the thalamus. (The habenula is the chief relay nucleus of the descending dorsal diencephalic conduction system.) This pathway is a part of the brain that is not well understood.

The researchers administered nicotine to rats for five days through a mini-pump inserted under their skin. At high doses of nicotine, the degeneration was almost complete in the pathway.

"We initially gave relatively high doses of nicotine, and then reduced it to a dose that induces plasma levels of nicotine in rats comparable to those of two-pack-a-day smokers," Ellison said. "Even at this much lower dose, we still found degeneration in the tract. We measured the degeneration and found that the larger the dose, the more damage."

Ellison's research team includes his UCLA graduate students Janice Carlson and Brian Armstrong, and Robert Switzer of NeuroScience Associates.

Ellison has studied the effects of drugs on the brain for more than 20 years. His research is funded by the National Institute of Drug Abuse and the Tobacco Related Disease Research Program, which is funded by California's tobacco tax.