The research is being published the week of October 1, 2007, in an advance, online issue of the journal Proceedings of the National Academy of Sciences (PNAS).
The new study reveals that, in rats, chronic nicotine use recruits a major brain stress system, the extrahypothalamic corticotropin releasing factor (CRF) system, which contributes to continued tobacco use by exacerbating anxiety and craving upon withdrawal.
The researchers found that administering a compound that blocked the receptors involved in this stress system alleviated withdrawal symptoms.
“We reduced the need to take nicotine by blocking CRF-1 receptors in the brain,” says Olivier George, a research associate in the Scripps Research Koob lab who conducted the study with Sandy Ghozland and other colleagues. “We were surprised by the compound's dramatic effectiveness. We don't know yet if the same mechanism is involved in humans with tobacco dependence, but it is very promising.”
Tobacco addiction is the leading avoidable cause of disease and premature death in the United States, responsible for more than 438,000 deaths annually, according to the Centers for Disease Control and Prevention. Nicotine, the main psychoactive ingredient in tobacco, is a tough drug, with smokers continuing to crave it long after they've started withdrawal. Most smoking-cessation medication is based on nicotine replacement therapy, using nicotine gum or patches, that substitutes one source of nicotine for another. Roughly 80 percent of smokers who try to quit relapse within a year.
While nicotine can produce mildly pleasurable effects, the Scripps Research scientists believe a more important factor in the difficulty in quitting is the brain's adaptation to that reward, which produces an intense discomfort upon withdrawal.
“The key in nicotine addiction is that the positive pleasurable effects of nicotine are instantaneous and short lasting, while the negative effects are delayed and long lasting,” George says. “Even if nicotine may transiently induce a relief from a negative emotional state, its long-term consequences are disastrous.”
For years, scientists have wanted to know what changes in the brain occur in the transition from nicotine use to nicotine dependence. In the current study, the researchers set out to see if nicotine dependence is linked to changes in the CRF system in the amygdala, an area of the brain that plays a primary role in the processing and memory of emotional reactions. The CRF system is activated by CRF-1, an essential protein for coping with stressful events.