Neutralizing nicotine?

Nicotine is believed to alter brain chemistry by increasing the level of dopamine, a neurotransmitter linked to pleasure and reward responses in humans. However, researchers are also finding that nicotine stimulates other brain chemicals, such as norepinephrine and serotonin.

To treat the addiction, according to Wynne Schiffer, a doctoral student in the neurobiology department at the State University of New York, Stony Brook, the chemical response associated with an addictive drug such as nicotine needs to be controlled, while sparing the response linked to everyday events that stimulate pleasurable reactions in the brain. If the chemical response is controlled, then the dopamine level will remain steady and not increase; therefore, the rewarding effect will be blocked and it will be easier for smokers to stop abusing nicotine.

In the study led by Schiffer, a group of rats was injected with topiramate and a control group was injected with saline (Synapse 2001, 42, 196–198). Researchers then gave both groups an acute dose of nicotine and measured the levels of dopamine, norepinephrine, and serotonin in the brain. Brain chemical levels were also examined in two additional groups: a group of rats given topiramate but not nicotine, and another group given topiramate but pretreated with nicotine 14 days before the experiment. This last “preaddicted” group served as the model for humans addicted to nicotine.

The rats given the saline and then nicotine showed a significant increase in all three chemicals in the brain, while the preaddicted rats showed an even greater increase in these brain chemicals—similar to what might occur in a smoker who has a cigarette after a period of not smoking.

However, nicotine-related increases of norepinephrine and dopamine were completely blocked in those rats treated with topiramate, and dopamine elevation in the preaddicted rats was significantly modified. However, topiramate did not drastically influence the effect of nicotine on serotonin.

“Our next series of studies will include more extensive investigations of the effects of topiramate on drug reward and drug-seeking behaviors,” says Schiffer.