期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 300, 期 1, 页码 124-133出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.300.1.124
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资金
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA014247] Funding Source: NIH RePORTER
- NIDA NIH HHS [DA14247] Funding Source: Medline
Offspring of women who smoke during pregnancy show behavioral abnormalities, including increased incidence of attentional deficit, learning disabilities, and cognitive dysfunction. Animal models indicate that nicotine elicits changes in neural cell replication and differentiation, leading to deficits in synaptic neurochemistry and behavioral performance, many of which first emerge at adolescence. We evaluated cellular morphology and regional architecture in the juvenile and adolescent hippocampus and the somatosensory cortex in rats exposed to nicotine prenatally. Pregnant rats were given nicotine throughout gestation via minipump infusion of 2 mg/kg/day, a regimen that elicits nicotine plasma levels comparable with those found in smokers. On postnatal days 21 and 30, brains were perfusion-fixed, coronal slices were taken between the anterior commissure and median eminence, and the morphology of the dorsal hippocampus and somatosensory cortex was characterized. In the hippocampal CA3 region and dentate gyrus, we found a substantial decrease in cell size, with corresponding decrements in cell layer thickness, and increments in cell packing density. Smaller, transient changes were seen in CA1. In layer 5 of the somatosensory cortex, although there was no significant decrement in the average cell size, there was a reduction in the proportion of medium-sized pyramidal neurons, and an increase in the proportion of smaller, nonpyramidal cells. All regions showed elevated numbers of glia. Taken together with previous work on neurochemical and functional defects, these data demonstrate that prenatal nicotine exposure compromises neuronal maturation, leading to long-lasting alterations in the structure of key brain regions involved in cognition, learning, and memory.
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