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Nicotine causes age-dependent changes in gene expression in the adolescent female rat brain

Center for Biomedical Genomics and Informatics, George Mason University, Discovery Hall, mail stop 1J1, 10900 University Blvd., Manassas, VA 20110, USA.
Neurotoxicology and Teratology (Impact Factor: 3.22). 01/2007; 29(1):126-40. DOI: 10.1016/j.ntt.2006.11.005
Source: PubMed

ABSTRACT Humans often start smoking during adolescence. Recent results suggest that rodents may also be particularly vulnerable to nicotine dependence during adolescence. We examined the effect of chronic nicotine exposure on gene expression profiles during adolescence in female rats, who were dosed with nicotine (and control animals were dosed with saline) via subcutaneously implanted osmotic minipumps. Brain samples were collected at four ages: before puberty (postnatal day 25), at about the time of puberty in females (postnatal day 35), and after puberty (postnatal days 45 and 55). The expression of 7931 genes in three brain areas was measured using DNA microarrays. Quantitative RT-PCR was also employed to confirm the expression patterns of selected genes. We used a novel clustering technique (principal cluster analysis) to classify 162 nicotine-regulated genes into five clusters, of which only one (cluster A) showed similar patterns of gene expression across all three brain areas (ventral striatum, prefrontal cortex, and hippocampus). Three clusters of genes (A, B, and C) showed dramatic peaks in their nicotine responses at the same age (p35). The other two clusters (D1 and D2) showed smaller peaks and/or valleys in their nicotine responses at p35 and p45. Thus, the age of maximal gene expression response to nicotine in female rats corresponds approximately to the age of maximal behavioral response and the age of puberty.

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    • "This may suggest that exposure to nicotine in high-activity neurodevelopmental periods may exert more deleterious effects than in adulthood. It is possible that chronic administration of nicotine, via altered nAChR activity, may influence gene expression and plasticity in the medial PFC and amygdala (Brown and Kolb 2001; Li et al. 2004; Polesskaya et al. 2007). This interaction may underpin the lack of extinction learning displayed in rats that are exposed to chronic nicotine (Eppolito et al. 2010). "
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    • "This may suggest that exposure to nicotine in high-activity neurodevelopmental periods may exert more deleterious effects than in adulthood. It is possible that chronic administration of nicotine, via altered nAChR activity, may influence gene expression and plasticity in the medial PFC and amygdala (Brown and Kolb 2001; Li et al. 2004; Polesskaya et al. 2007). This interaction may underpin the lack of extinction learning displayed in rats that are exposed to chronic nicotine (Eppolito et al. 2010). "
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    • "Alterations of dendritic structure in some medial prefrontal cortical neurons have been reported following adolescent nicotine administration (Bergstrom et al., 2008). Moreover, adolescent nicotine exposure has been shown to produce changes in gene expression in the hippocampus and prefrontal cortex (Polesskaya et al., 2007). Collectively, these findings suggest that nicotine may induce long-term neural changes that could impact cognitive processes involving the hippocampus and prefrontal cortex. "
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