exposure to low levels of nicotine, as little as that in a single
cigarette, can cause lasting changes in the brain's 'reward' areas,
report two University of Chicago Medical Center researchers in
the October 2000 issue of the journal Neuron.
researchers discovered that nicotine uses a mechanism responsible
for learning and memory to enhance the connections between one
set of nerve cells that are sensitive to the drug and other nerve
cells that register pleasure. They also demonstrate that the first
exposure to nicotine can induce an enduring "memory trace," amplifying
the drug's pleasing effects and boosting the desire to repeat
uncovering the precise cellular mechanisms of nicotine's effect,
the study suggests new, more precise targets for drugs designed
to block the powerful craving.
appears to be the crucial first step in the process of addiction,"
says neurobiologist Daniel McGehee, assistant professor in anesthesia
and critical care and the study's director. "Now that we know
how this happens, we can begin to search for better ways to intervene."
reinforcing effect of nicotine is the primary reason people cannot
quit smoking, despite widespread awareness that smoking causes
cancer, heart disease, stroke, emphysema, bronchitis, vascular
disease, cataracts, impotence, and many other health problems.
Nicotine dependence is estimated to cause 70 times more deaths
in the United States than all other types of drug dependence combined.
addiction makes millions of people suck carcinogens into their
lungs over and over again, day after day," says McGehee. "If this
knowledge leads to new ways of helping people quit successfully,
it will be an important step for public health worldwide."
brain reward areas serve to acknowledge and reinforce beneficial
behaviors-for example, eating when you're hungry. The system encourages
the body to repeat pleasing behaviors by releasing dopamine, the
neurotransmitter associated with the pleasant feelings, in the
reward areas. "That was good," is the basic message of increased
dopamine levels. "Do it again."
drugs of abuse, like nicotine, can usurp the pathways, also stimulating
the release of dopamine. McGehee and post-doctoral researcher
Huibert Mansvelder, working with brain tissue from rats, demonstrated
how nicotine takes control of the reward pathways. Nicotine alters
neuron connections using a process similar to the cellular mechanisms
underlying the creation of memory.
appears to cause addiction by strengthening the excitatory connections
on the neurons that make dopamine, which are found in the Ventral
Tegmental Area (VTA) of the brain reward center. More excited,
the neurons release more dopamine in the reward areas.
cellular locus of addiction is farther "upstream" in the reward
pathway than anticipated. McGehee and Mansvelder found that nicotine's
lasting effects result from the drug's interaction with a receptor
on the synaptic endings, the part of the cell that sends the signals.
When these endings are exposed to nicotine, there is a direct
increase in the excitatory signal transmitted onto the dopamine
neurons, which then increases dopamine release.
stimulates neurons by attaching to a specific structure on the
neuron, called the nicotinic acetylcholine receptor. There are
many different nicotinic acetylcholine receptors, performing various
roles throughout the body. But the good news is that the addictive
process appears to involve only one subtype, acetylcholine receptors
containing the alpha7 subunit, making it a potential target for
medications that could help smokers kick the habit.
we can do to discover even a slightly more effective method to
help people stop smoking," adds McGehee, "can have a tremendous