by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

Nicotine is a highly addictive drug and kicking the smoking habit has proven to be extremely difficult for many cigarette smokers.

Several smoking cessation strategies work reasonably well in the short term (3 months or so) but relapse rates are greater than 80% after 1 year.  There are a variety of reasons why smokers relapse but a strong relapse predictor is body weight gain, particularly in women.

Nicotine does decrease body weight and it does so by several mechanisms.  Nicotine acts in the brain to inhibit the brain regions that regulate appetite.  Nicotine also acts on fat cells to stimulate fat breakdown and it also stimulates energy expenditure (metabolism) by cells throughout the body.  Without nicotine onboard, appetite increases, fat breakdown and metabolism decrease and before you know it, the ex-smoker has put on 10 or more pounds.  After a peak in the mirror, the ex-smoker becomes a former ex-smoker.  If there was some way to prevent the weight gain, smoking relapse rates would likely fall and this would be beneficial for the individual smoker and for the overall health profile of the U.S population.

Science Magazine cover

A new study published in Science magazine may provide some hope that the appetite and body weight gain can becontrolled in the abstinent smoker.  These studies were done in mice where food intake and body weight were monitored after treatments which stimulated or blocked receptors for nicotine were tested.

Nicotine does have specific targets (receptors) in the brain where it produces its addictive actions.  The nicotinic receptors are found on neurons in the ventral tegmental area that use dopamine as a neurotransmitter and these neurons are in the reward pathways in the brain.  However, receptors for nicotine are also found in a region of the brain called the hypothalamus which is responsible for regulating appetite (among other things).  The study in Science revealed that the nicotinic receptors were found on a subset of neurons called POMC neurons and nicotine and a related drug activated these neurons.  POMC is an abbreviation for a protein known as pro-opiomelanacortin.  This in an interesting protein because it breaks down into three important smaller proteins: endorphin (the body’s natural opiate), melanocortin and adrenoccorticotrophin (which stimulates the adrenal gland).  The connection between endorphin and adrenocorticotrophin and nicotine induced appetite regulation was not investigated in this study.  However, it looks like melanocortin may be a key player here because when receptors for melanocortin were “knocked down” nicotine was no longer able to suppress feeding in these mice.

These studies were done in mice and there is a long way to go before these results can be translated into safe and effective treatments for nicotine addiction in human smokers.

These studies were also done in nicotine naïve mice; they were not nicotine addicted.  It is known that nicotine changes the nervous system in nicotine-addicted mice and humans so the role of melanocortin in appetite regulation needs to be studied in nicotine addicted mice.  However, these studies do provide new and important data about the complex mechanisms that regulate appetite and feeding behaviors and how these mechanisms may overlap with the reward pathways in the brain.  This could eventually lead to effective suppression of appetite in nicotine abstinent smokers leading to more appealing reflections in the mirror.