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Anti-epileptic drug blocks nicotine's effects on brain chemistry

21 November, 2001

A study has shown that the anti-epileptic drug topiramate can block some of the nicotine-triggered changes in brain chemistry, and may have potential for the treatment of nicotine addiction in humans.

Nicotine is widely believed to trigger dependence by elevating certain brain chemicals associated with pleasure and reward. 

"This treatment strategy uses a drug that simultaneously targets two different neurotransmitter pathways, thereby reducing the neurochemical activity believed to underlie nicotine addiction," said Wynne Schiffer, lead author of the study which took place at at the U.S. Department of Energy's Brookhaven National Laboratory.

Brookhaven scientists have been studying the neurochemistry of drug addiction for nearly two decades, and have used information gathered from these studies to investigate potential pharmacologic treatments for drug abuse. Previous studies focused on agents that block drug-induced increases in brain dopamine, a neurotransmitter associated with pleasure and reward.

"But new theories about nicotine dependence suggest that dopamine isn't the only system involved," said Stephen Dewey, a coauthor on the study. For example, nicotine stimulates specific excitatory systems in the brain, and these systems excite not only dopamine but a host of other brain chemicals, such as norepinephrine and serotonin.

In the current study, the results of which are being published in the journal Synapse, scientists injected one group of rats with topiramate while another group received control injections of saline. The scientists then gave both groups an acute dose of nicotine and measured dopamine, norepinephrine, and serotonin levels in their brains. Animals given topiramate but no nicotine were also studied to see if topiramate alone had any effect on the neurotransmitters. The scientists also tested the effect of topiramate on dopamine in animals that had been pretreated with nicotine for 14 days prior to the experiment, to serve as a model for humans addicted to the drug.

As expected, animals that received saline and then nicotine showed significant increases in all three brain chemicals. Rats that had been previously "addicted" to nicotine showed even greater elevations in brain dopamine than those that received just the acute dose - similar to what you'd expect to see in a smoker who has a cigarette after a period of not smoking.

Pretreatment with topiramate, however, completely blocked nicotine-triggered increases in norepinephrine and dopamine -- and even modulated the dopamine response in the "addicted" animals.

"Since the brain's dopamine and norepinephrine systems are closely linked, the ability of topiramate to reduce increases in both neurotransmitters suggests that this drug has potential for treating nicotine abuse" Schiffer said.