NEW YORK (Reuters) -- Long-term nicotine exposure has effects on the areas of the brain involved in motivation, according to the results of a study conducted in rats. The discovery may help explain why people become addicted to nicotine, say researchers at the Scripps Research Institute in La Jolla, California.
The booming market for smoking cessation aids such as nicotine patches and gums is testament to the fact that nicotine addiction is a hard habit to break because it's just that, an addiction. But until now, researchers had little understanding of the biologic events that take place during nicotine withdrawal, pushing smokers who are trying to quit into relapse.
The study, published Thursday in the journal Nature, indicates that changes in brain "reward mechanisms" are altered in rats undergoing nicotine withdrawal, at a magnitude similar to that which has been observed during withdrawal from other addictive drugs. Decreases in brain reward function occur in individuals addicted to drugs like cocaine, opiates and alcohol, causing depression, anxiety and irritability and increasing the risk of relapse, in essence to self-medicate for these symptoms.
Dr. Athina Markou and her team at Scripps studied rats who had implanted subcutaneous pumps dispensing either saline (control) or a dosage of nicotine sufficient to maintain blood nicotine levels comparable to those measured in individuals who smoke 30 cigarettes a day. After removal of the pumps (withdrawal), the researchers measured changes in intracranial self-stimulation (ICSS) thresholds in the rats' brains. These thresholds tend to increase as brain reward function decreases.
Rats undergoing nicotine withdrawal demonstrated significant elevations in ICSS thresholds -- significant decreases in brain reward function -- within 4 hours of pump removal, peaking at 6 to 8 hours. These changes in brain reward function persisted for 4 days and were similar in magnitude to changes in reward function known to "motivate" those in withdrawal from other addictive drugs into relapse. On day 5 after removal of the pumps, mean brain reward function levels returned to baseline.
The Scripps team also found in a subgroup of the nicotine-treated rats that injections of a nicotine antagonist -- which blocks nicotine from eliciting "positive" effects through its receptors in the brain -- led to dose-dependent increases in brain reward thresholds. This indicates that during withdrawal from nicotine, the biologic changes that cause depression and other affective symptoms are, at least in part, mediated by changes in nicotine receptors in the brain.
Markou told Reuters that the implications of these findings for smoking cessation are twofold. First, the data show that "...nicotine is as addictive as other drugs of abuse such as morphine, cocaine, amphetamines and alcohol." Second, "...during withdrawal from any of these drugs of abuse, there are emotional and affective symptoms that drive the person back..." to the addiction.
Markou also said in the interview that smokers who understand that the depression, anxiety and irritability that they experience when trying to quit are normal and transient symptoms may be better equipped to cope with the emotional aspects of withdrawal and maintain abstinence.
SOURCE: Nature (1998;393:76-79)
