Prenatal exposure to nicotine increases risk of apnea in brains of ne...( ulated. In the rat model used by the r...)

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.
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Federation of American Societies for Experimental Biology
12-Apr-2003