Striking phenotypic similarities have been noted between infants exposed to toluene in utero and infants diagnosed with fetal alcohol syndrome. However, data are lacking to relate the degree of maternal exposure to toluene and other inhalant drugs of abuse to their effects on the fetus. This is an important issue because a majority of persons who abuse inhalants are females in their prime childbearing years, and the National Pregnancy and Health Survey has indicated that 12,000 pregnant women each year abuse inhalants. There are no quantitative data on transplacental transfer of toluene or any other inhalants in humans, although rodent studies indicate that 10% of an inhaled dose of toluene reaches the fetus whereas this fraction is 2% -4% for chlorinated hydrocarbons or for more highly substituted aromatics such as xylene and styrene. The proposed work builds on our previous extensive neuroimaging studies of drugs of abuse using positron emission tomography (PET) and high-field magnetic resonance spectroscopic imaging, and our recent preliminary preclinical studies with the abused inhalant, toluene, labeled with the PET radioisotope carbon-11. The objective is to develop methodologies for quantifying exposure of fetal macaques after administration of the positron labeled inhalants [11C] toluene and [11C] butane to the macaque mother. This work with two inhalants with somewhat different physical properties and reported subjective effects will set the stage for hypothesis driven PET studies with these and other inhalants in pregnant non-human primates. Ultimately, the hope is to relate the mother's exposure to inhalants to the dose received by the fetus and to post-natal behavioral deficits.
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