Abreu-Villaça Yael, Seidler Frederic J, Tate Charlotte A, Cousins Mandy M, Slotkin Theodore A
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Neuropsychopharmacology. 2004 May;29(5):879-90. doi: 10.1038/sj.npp.1300401.
Maternal smoking during pregnancy increases the likelihood that the offspring will become smokers in adolescence. In the current study, we evaluated effects of prenatal and adolescent nicotine exposure in rats to assess whether there is a biological basis for this relationship. Pregnant rats were given nicotine or vehicle throughout pregnancy and the offspring then again received nicotine or vehicle during adolescence (postnatal days PN30-47.5), using a regimen (6 mg/kg/day by subcutaneous infusion) that produces plasma nicotine levels similar to those in smokers. Evaluations were made in the cerebral cortex and midbrain during adolescent nicotine administration (PN45) and for up to 1 month after the end of treatment. We assessed the magnitude and persistence of nicotinic acetylcholine receptor (nAChR) upregulation; in addition, we evaluated cholinergic synaptic activity by comparing the effects on choline acetyltransferase (ChAT), a constitutive marker for cholinergic nerve terminals, with those on hemicholinium-3 (HC-3) binding to the presynaptic choline transporter, which is regulated by nerve impulse activity. Prenatal nicotine exposure had only minor effects on nAChRs but produced persistent cholinergic hypoactivity (reduced HC-3 binding relative to ChAT) throughout adolescence and into adulthood (PN75). Adolescent nicotine exposure evoked robust nAChR upregulation and also suppressed cholinergic activity. Prenatal nicotine exposure reduced the upregulation of nAChRs evoked by adolescent nicotine but worsened the cholinergic hypoactivity during withdrawal. Our results indicate that prenatal nicotine exposure alters the subsequent response to nicotine in adolescence, effects that may contribute to the association between maternal smoking during pregnancy and subsequent adolescent smoking in the offspring.
孕期母亲吸烟会增加后代在青春期成为吸烟者的可能性。在本研究中，我们评估了产前和青春期尼古丁暴露对大鼠的影响，以评估这种关系是否存在生物学基础。在整个孕期给怀孕大鼠注射尼古丁或赋形剂，然后在青春期（出生后第PN30 - 47.5天）再次给后代注射尼古丁或赋形剂，采用一种（皮下输注6毫克/千克/天）能产生与吸烟者相似血浆尼古丁水平的给药方案。在青春期尼古丁给药期间（PN45）以及治疗结束后长达1个月的时间里，对大脑皮层和中脑进行评估。我们评估了烟碱型乙酰胆碱受体（nAChR）上调的程度和持续性；此外，我们通过比较对胆碱乙酰转移酶（ChAT，胆碱能神经末梢的组成性标志物）的影响与对半胱氨酸转运体-3（HC - 3）与突触前胆碱转运体结合的影响来评估胆碱能突触活性，后者受神经冲动活动调节。产前尼古丁暴露对nAChRs仅有轻微影响，但在整个青春期直至成年期（PN75）均产生持续性胆碱能活动减退（相对于ChAT，HC - 3结合减少）。青春期尼古丁暴露引起强烈的nAChR上调，同时也抑制了胆碱能活性。产前尼古丁暴露减少了青春期尼古丁引起的nAChRs上调，但在戒断期间使胆碱能活动减退加剧。我们的结果表明，产前尼古丁暴露改变了青春期对尼古丁的后续反应，这些影响可能有助于解释孕期母亲吸烟与后代随后青春期吸烟之间的关联。
