Public Release: 

Prenatal exposure to nicotine increases risk of apnea in brains of newborn rats

Federation of American Societies for Experimental Biology

University of Arizona researchers report new evidence that exposure to nicotine in the developing rat fetus enhances the function of GABAa receptors, a key component of brain cells that control breathing rhythm. The increased functional capacity of the GABAa receptors may make these newborns more likely to have episodes of apnea, in which breathing simply stops.

Zili Luo, MD, Ph.D., a postdoctoral fellow in the laboratory of Dr. Ralph Fregosi, describes the study at the Experimental Biology 2003 meeting in San Diego, as part of the American Physiological Society program.

In humans, cases of Sudden Infant Death Syndrome (SIDS) occur most often in infants between the ages of two and four months, while the baby is sleeping. SIDS deaths usually are attributed to apnea or the cessation of breathing and the failure of the infant to self-resuscitate or resume breathing. Smoking during pregnancy has been found to increase the risk of Sudden Infant Death Syndrome (SIDS) by about five fold, and researchers have long been eager to pinpoint the mechanism by which this occurs.

Earlier studies by other investigators showed that prenatal nicotine exposure enhances the function and density of GABAa receptors in the cortex, hippocampus and other areas of the brain. These observations led the Fregosi laboratory to hypothesize that prenatal nicotine exposure may also alter the function or density of the GABAa receptors on cells in the brain regions that control breathing. In earlier work, the Fregosi laboratory had already sown that pharmacological stimulation of these inhibitory nerve cell membrane receptors led to slowing of the breathing rate, with intense stimulation leading to cessation of breathing altogether.

This study looked at whether prenatal nicotine enhances the function of these receptors, thus making it more likely that newborns that had been exposed to nicotine would have more episodes of apnea when the GABAa receptors are stimulated. In the rat model used by the researchers, both things proved true.

Pregnant rats were given either saline (the control group) or a nicotine dose calculated to result in blood levels of nicotine equivalent to those found in a human smoking two packs of cigarettes per day. The rats were given saline or nicotine from the fifth day of pregnancy through the day of delivery (21 days in a rat). Newborn rat pups aged from one to four days were deeply anesthetized, then the brain stem and spinal cord were removed and placed in a plasma-like solution with oxygen, a method that allows the researchers to measure breathing rhythm in a highly controlled setting. This method also allows the addition of drugs and other chemicals to examine how various agents change the breathing rhythm.

Breathing rates recorded from the brain stem-spinal cord preparation of both the nicotine-exposed and the saline-exposed rats were measured for half an hour, and then both preparations were bathed in varying doses of either pentobarbital sodium (Nembutal) or muscimol for 30 minutes.

These drugs stimulate GABAa receptors, and they did decrease the rate of breathing in both the nicotine-exposed and saline-exposed brains, as predicted. But the brains of the pups that had been exposed to nicotine during fetal development consistently responded with a greater reduction in breathing rates. In fact, in many cases the same drug doses that caused only marginal slowing in the brains that had not been exposed to nicotine proved to cause apnea, complete cessation of breathing, in the brains that had been exposed to nicotine.

Dr. Fregosi says this provides important evidence that prenatal nicotine exposure increases the functional capacity or density of the GABAa receptors on neurons that control breathing. This suggests that prenatal nicotine exposure is a factor making human infants more likely to have frequent, longer-lasting, and perhaps fatal episodes of apnea. The laboratory is now conducting other experiments designed to determine if indeed the GABAa receptor density is increased by prenatal nicotine exposure on cells that are known to be important in the control of breathing and to determine if other properties of these cells are altered by the nicotine exposure.


(American Physiological Society)

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.