Nicotine Addiction: Influence of Prenatal and Adolescent Exposure

尼古丁成瘾：产前和青少年时期接触尼古丁的影响

• 批准号: 7596961
• 负责人: Robert Nelson Pechnick
• 金额: $ 32.5万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596961
• 关键词: Address; Adolescence; Adolescent; Adult; Adult Children; Adverse effects; Affect; Cause of Death; Cocaine; Development; Dose; Drug Kinetics; Drug usage; Environmental Tobacco Smoke; Exposure to; Fetal Development; Gene Expression; Genes; Individual; Intervention; Laboratory Animals; Lead; Long-Term Effects; Maintenance; Measures; Neurobiology; Nicotine; Nicotine Dependence; Plasma; Pregnancy; Pregnant Women; Property; Rattus; Self Administration; Smoke; Smoking; Testing; Tobacco smoke; United States; cigarette smoking; critical developmental period; critical period; epidemiologic data; fetal tobacco exposure; gene repression; in utero; knowledge base; neurobehavioral; neurochemistry; neurotransmission; nicotine abuse; nicotine gum; nicotine patch; offspring; prenatal; prenatal exposure; prenatal influence; research study; response; treatment strategy

DESCRIPTION (provided by applicant): Nicotine is implicated in many of the adverse effects of smoking on pregnancy and fetal development. Besides the pathophysiological consequences, epidemiologic data indicate that individuals exposed to tobacco smoke in utero are more likely to abuse nicotine as adults. Adolescence also is a period of vulnerability to nicotine. Currently, the neurobiological factors underlying the initiation and maintenance of nicotine addiction are not known; this is a critical gap in our knowledge base. Our preliminary studies show that prenatal exposure to nicotine produces long-term effects on nicotine self-administration and the expression of genes related to GABAergic neurotransmission. Our proposed experiments build upon these findings and will generate new and potentially important information on the influence of prenatal and/or adolescent nicotine exposure on nicotine self-administration in the adult rat. Experiment #1 will characterize further the effects of prenatal nicotine exposure on nicotine self-administration in the adult rat. The threshold dose of prenatal nicotine required to alter adult nicotine self-administration will be determined in order to ascertain the consequences of exposure to second-hand smoke. Experiment #2 will test the hypothesis that combined prenatal and peripuberal exposure to nicotine will lead to greater increases in nicotine self- administration, compared to prenatal exposure alone. We also will find whether the peripuberal period is a critical period of vulnerability to nicotine. A critical question is whether exposure to nicotine during development affects only the responses to nicotine. Experiment #3 will test the hypothesis that prenatal and/or peripuberal exposure to nicotine also increases cocaine self-administration. Experiment #4 will begin to elucidate the mechanisms underlying increased nicotine self-administration by evaluating changes in genes related to GABAergic neurotransmission as a consequence of prenatal and/or peripuberal exposure to nicotine. Relevance: Our experiments will yield critical information that might impact the development and implementation of appropriate pharmacologic treatment and intervention strategies for nicotine addiction. In addition, the results may identify potential long-term and potential deleterious effects of current treatment strategies. Using a nicotine patch or nicotine gum to treat pregnant women might reduce their smoking, but increase the vulnerability of their offspring to develop nicotine addiction.

描述（由申请人提供）：尼古丁与吸烟对妊娠和胎儿发育的许多不利影响有关。除病理生理后果外，流行病学数据表明，在子宫内暴露于烟草烟雾的人更有可能滥用成年人。青春期也是尼古丁的脆弱时期。当前，尚不清楚尼古丁成瘾的启动和维持的基础的神经生物学因素。这是我们知识库中的关键差距。我们的初步研究表明，产前暴露于尼古丁会对尼古丁自我给药以及与GABA能神经传递相关的基因的表达产生长期影响。我们提出的实验以这些发现为基础，并将生成有关产前和/或青春期尼古丁对成年大鼠尼古丁自我给药的影响的新的重要信息。实验＃1将进一步表征产前尼古丁暴露对成年大鼠尼古丁自我给药的影响。为了确定暴露于二手烟的后果，将确定改变成年尼古丁自我给药所需的产前尼古丁的阈值剂量。实验＃2将检验以下假设：与仅产前暴露相比，与尼古丁相比，在产前和周围暴露于尼古丁的联合会导致尼古丁自我给药的增加。我们还将发现围骨时期是否是尼古丁脆弱的关键时期。一个关键的问题是，发育过程中对尼古丁的暴露是否仅影响对尼古丁的反应。实验＃3将检验以下假设：尼古丁产前和/或周围暴露还会增加可卡因自我给药。实验＃4将开始通过评估与尼古丁产前和/或周围暴露于尼古丁的结果，通过评估与GABA能神经传递相关的基因的变化来阐明增加尼古丁自我给药的机制。相关性：我们的实验将产生关键信息，可能会影响尼古丁成瘾的适当药理治疗和干预策略的开发和实施。此外，结果可能会确定当前治疗策略的潜在长期和潜在有害影响。使用尼古丁斑块或尼古丁口香糖治疗孕妇可能会减少吸烟，但会增加其后代发展尼古丁成瘾的脆弱性。