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.
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