Smoking causes long lasting changes to brain's bio chemistry

New research shows for the first time that smoking produces long-lasting biochemical changes in the human brain similar to those changes previously seen in the brains of animals that used cocaine, heroin, and other illicit drugs.

This new research supports the idea that long-term smoking alters the brain in ways that contribute to addiction, and provides insight into how addiction works, says lead author Bruce Hope, PhD, of the National Institute on Drug Abuse (NIDA). The study, supported by NIDA, is published in the February 21 issue of The Journal of Neuroscience.

"The data show that there are long lasting chemical changes in the brains of humans," says Michael Kuhar, PhD, of Emory University. "The chemical changes alone suggest a physiological basis for nicotine addiction." Kuhar was not involved in this study.

Hope and his colleagues studied samples of human brain tissue from the nucleus accumbens and the ventral midbrain, brain regions that play a part in controlling addiction-related behaviors. Eight samples were taken from each of three groups: long-term smokers until the time of death, previous long-term smokers, and nonsmokers. All died of causes not related to smoking.

The researchers analyzed levels of two specific enzymes found inside neurons that translate chemical signals outside the neuron, such as the neurotransmitter dopamine, into chemical signals and changes inside the neuron. They found elevated levels of these enzymes in the smokers, but, more interesting, levels remained high, as compared to nonsmokers, in the ventral midbrains of former smokers. This suggests that the changes persist long after smoking has ceased and could contribute to drug relapse, Hope says.

"The parallel between the new study and the animal studies is important because a causal role has been shown in animal studies between increased levels of these neuronal signaling enzymes in these brain regions and addiction-related behaviors. This strongly suggests that the similar changes observed in smokers and former smokers contributed to their addiction," he adds.

Hope points out that although previous investigations on human smokers revealed similar results, "these biochemical changes have not yet been observed to play causal roles in addiction-related behaviors, or were altered in brain regions where their effects on behavior are unknown."

Hope BT, Nagarkar D, Leonard S, Wise RA.
Long-Term Upregulation of Protein Kinase A and Adenylate Cyclase Levels in Human Smokers
J. Neurosci. 2007 27: 1964-1972; · [Abstract]