Nicotine has significant effects on brain GABA

Dec 10 2007

There is a clear link between GABA - a chemical substance of the central nervous system that inhibits neurons in the brain - and nicotine dependence, according to a study presented at the American College of Neuropsychopharmacology (ACNP) annual meeting.

Researchers discovered that nicotine has significant effects on brain GABA, a finding which could potentially help curb the pleasurable effects of nicotine and help people break their addiction to it.

“We found that GABA may provide a very useful target for nicotine addiction therapies,” said Graeme Mason, Ph.D., associate professor in the Magnetic Resonance Research Center in the Departments of Diagnostic Radiology and Psychiatry at Yale University School of Medicine and an ACNP member. “GABA is just one of a complex network of actors that promotes addiction, and we're hoping that this research will ultimately lead us to ways to help people quit smoking.”

Mason sought to discover whether the enjoyable effects associated with smoking could be reduced in some way. When people use nicotine they may experience a sensation of reward, diminished anxiety, or a belief that they can focus more clearly or learn more easily. Researchers wanted to explore how a specific type of neuron that releases dopamine, a chemical that has been associated with pleasure, can prolong and intensify the pleasurable effects of nicotine. Although GABA inhibits those neurons, nicotine works against the ability of GABA to inhibit dopamine neurons after about 20 minutes, so the gratifying effects of nicotine are prolonged.

Researchers gave people who smoked regularly nicotine inhalers that deliver the same amount of the drug as in one cigarette. The amount of GABA in the subjects' brains rose about 10%, but the brain was found to make GABA four times faster after using the inhalers, and the rate of new GABA generation remained high for at least 45 minutes. In other words, keeping the supply of GABA levels high has the potential to reduce the pleasurable effects of smoking, in terms of duration and intensity.

“While GABA is probably not the root of nicotine addiction, it is part of a complex network of actors that are involved in addiction,” Mason says.

Another study presented at the ACNP annual meeting which explored the role of GABA, genetics and environmental factors in smoking found that tobacco addiction is at least 50% determined by genetics. For this reason, researchers may be able to identify individuals who are vulnerable to nicotine dependence, and then implement prevention strategies accordingly.

For this study, Ming Li, Ph.D., Professor of Genetics in Psychiatry and Neurosciences at the University of Virginia recruited more than 2000 participants representing more than 600 families of smokers. They examined different regions on various chromosomes that showed linkage to nicotine addiction. Then they searched for susceptibility genes within these regions that appear to be associated with addiction. Some of these are the GABA-B receptor subunit 2 (GABAB2) gene on chromosome 9, and the GABA-A receptor-associated protein (GABARAP) gene on chromosome 17.

Li says the research could have significant public health implications because it could help curb smoking rates since researchers may be able to predict who is more prone to nicotine addiction. Tobacco is one of the most widely used substances; it kills more than 435,000 Americans each year, and despite increasing public awareness of the health risks associated with its use, little reduction in smoking prevalence has been achieved nationwide in recent years.