How nicotine may buffer the brain

Smokers who claim that tobacco relaxes them are reporting a documented biochemical effect. Nicotine, the main active compound of tobacco, lowers the perception of pain and physical stress by reducing the amount of the neurotransmitter dopamine that is broken down by neurons in the prefrontal cortex, a region of the brain that lies just behind the forehead. But Yale psychiatrist Tony P. George, M.D., and his colleagues report in the July issue of Neuropsychopharmacology that the dopamine pathways are not acting on their own. It appears that they are regulated by the brain’s system of endogenous opioid peptides—the brain’s own pain relievers.

The Yale group performed experiments in which rats were given small amounts of nicotine; some were also given naloxone, which blocks the action of endogenous opioid peptides, while others received an inactive saline solution. When the animals were tested by brief electrical shocks to the foot, the response of the saline group showed that nicotine had acted on the endogenous opioid peptides to reduce the amount of dopamine metabolized by prefrontal neurons, while the response of the naloxone group showed normal (non-nicotine) levels of dopamine metabolism. This indicates that the endogenous opioid system must participate in order for nicotine to be able to alter levels of dopamine uptake and thereby reduce perceptions of pain and stress.

Understanding the molecular basis of nicotine’s effects in the brain may give scientists new tools for developing ways to treat nicotine dependence. “Furthermore,” says George, “our results may have implications for our understanding of neuropsychiatric disorders such as schizophrenia,” in which smoking, excessive responses to stress, and some dysfunction of the prefrontal cortex all may be linked.