Effects of perinatal nicotine on the Brain
Abstracts
Initial Award Abstract |
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Numerous studies in animals have shown convincingly that exposure to nicotine, particularly during early development, produces profound effects on the brain. However, it has been very difficult to translate the results of these studies to humans because the brain, for obvious reasons, is not easily accessible for study in humans while they are alive. Recent developments in imaging technology might lessen this limitation. Proton magnetic resonance spectroscopy is a technology which is similar to a regular MRI procedure except that more details about tissue chemistry can be obtained. The proposed study in animals will determine if, indeed, we can assess the detrimental effects of nicotine exposure on the brain with this technology. Results of the study will provide the groundwork for implementing subsequent studies of a comparable nature in humans. |
Final Report |
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Numerous studies in animals have shown convincingly that exposure to nicotine, particularly during early development, produces profound effects on the brain. However, it has been very difficult to translate the results of these studies to humans because the brain, for obvious reasons, is not easily accessible for study in humans while they are alive. Recent developments in imaging technology might lessen this limitation. Proton magnetic resonance spectroscopy ('H MRS) is a technology which is similar to a regular MRI procedure except that more details about tissue chemistry can be obtained. In order to determine if the neurotoxic effects of nicotine on the brain could be detected by 'H MRS, pregnant rats were treated from day 5-21 of pregnancy with placebo or nicotine (6.0 mg/kg/day), a dose which produces plasma levels of nicotine comparable to those measured in smokers who smoke 3 packs of cigarettes/day. Pregnant rats also were treated with nicotine (0.3 mg/kg/day), a dose of nicotine which produces plasma levels similar to those measured in people exposed to "passive" or "secondhand" smoke.
Adult offspring showed dose, sex and region specific changes in brain biochemistry. Female offspring showed significant changes in a number of chemical compounds, particularly in the left side of the brain in an area called the hippocampus. Some of the effects were produced by both the high and low dosages. Male offspring showed significant changes in the amino acid GABA, particularly in left frontal cortex. These results confirm that prenatal nicotine exposure, even to very low dosages, can produce longterm (apparently permanent) effects on brain biochemistry. The results of this study have important public health implications. In addition, since these measures of brain chemistry can be detected in humans with 'H MRS, future studies can be performed to determine if comparable neurotoxic effects occur in humans exposed to nicotine during early development. |
