Behavioral Effects of Gestational Inhalant Abuse in Rats

妊娠期吸入滥用对大鼠的行为影响

• 批准号: 6773781
• 负责人: SCOTT E BOWEN
• 金额: $ 33.25万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773781
• 关键词: animal developmental psychology; behavioral /social science research tag; developmental neurobiology; developmental psychology; disease /disorder model; embryo /fetus toxicology; inhalation drug abuse; laboratory rat; learning; model design /development; neuropsychology; neurotoxicology; operant conditionings; psychomotor function; toluene

DESCRIPTION (provided by applicant): The abuse of inhalants is a significant public health problem throughout the U.S. and the world. There is a paucity of systematic examination of the short- and long-term developmental consequences of prenatal exposure to organic solvent inhalants. Because the youthful population abusing solvents includes many women in their childbearing years, there is concern about the potential negative impact of these inhalants on pregnancy outcome and the life-long physical and mental development of children. Indeed, there is emerging evidence of a Fetal Solvent Syndrome, which is a constellation of birth defects, and developmental delays that have been attributed to maternal abuse of organic solvent inhalants. Therefore, the aim of this proposed research is to investigate and develop an animal model of inhalant abuse in pregnant rodents to determine the range of developmental delays and biobehavioral birth defects caused by maternal abuse of organic solvent inhalants during pregnancy. This research will be informed by the current hypothesis that in humans a Fetal Solvent Syndrome has a profile of neurobehavioral effects similar to those produced by prenatal exposure to alcohol. A key objective of this research proposal is the design and implementation of a preclinical model of prenatal inhalant administration that mimics the episodic, high-dose exposure pattern in women who abuse toluene. We will characterize the maternal and fetal neurotoxic effects of toluene during specific "critical periods" of development that mimic distinct maturational stages of human brain development. We will examine the ontogeny and alteration of postnatal biobehavioral development and behavior in rats exposed in utero to toluene. This research with toluene will have important implications for understanding the impact of prenatal inhalant abuse of a variety of organic solvents and gaseous anesthetics on development and behavior. Furthermore, this research will generate a clinically relevant model with which neuroanatomical and biochemical outcomes, along with the mechanisms of prenatal inhalant abuse may be studied. Finally, this research has the potential to assist in the design of effective treatments for inhalant abuse.

描述（由申请人提供）：吸入剂是美国和世界各地的重大公共卫生问题。对产前暴露于有机溶剂吸入剂的短期和长期发育后果的系统检查很少。由于滥用溶剂的年轻人口包括许多妇女在生育时期，因此担心这些吸入剂对怀孕结果以及儿童终身身体和心理发展的潜在负面影响。确实，有新的证据表明胎儿溶剂综合征是出生缺陷的一个星座，而发育延迟归因于孕产妇滥用有机溶剂吸入剂。因此，这项拟议的研究的目的是调查和开发一种孕妇啮齿动物的动物模型，以确定由于孕妇在怀孕期间对有机溶剂吸收剂的孕产性滥用有机溶剂引起的发育延迟和生物行为的范围。当前的假设将告知这项研究，即在人类中，胎儿溶剂综合征具有与产前暴露于酒精相似的神经行为效应的特征。该研究建议的一个关键目的是设计和实施产前吸入式临床前模型，该模型模仿了滥用甲苯的女性中的情节性高剂量暴露模式。我们将表征甲苯在特定的开发“关键时期”中的母体和胎儿神经毒性作用，以模仿人脑发育的不同成熟阶段。我们将研究子宫内暴露于甲苯的大鼠的产后生物行为发育和行为的本体发育和改变。这项对甲苯的研究将对理解产前吸入式滥用各种有机溶剂和气态麻醉对发展和行为的影响具有重要意义。此外，这项研究将产生与临床相关的模型，可以研究神经解剖学和生化结果，以及可以研究产前吸纳滥用机制的模型。最后，这项研究有可能协助设计有效的吸入滥用治疗方法。