What are the neurobehavioral consequences of inhalant abuse by pregnant women for their offspring? It is surprising that almost no research has addressed this question, since inhalant abuse is well-recognized as a significant health problem, especially among both male and female teenagers. Inhalant abuse consists of self-administering agents for short durations at high concentrations, in contrast to chronic, low-level exposures that occur in the workplace or general environment. The agents frequently are complex mixtures that include volatile organic solvents as constituents, which are known to produce toxic effects, including neurobehavioral ones. Many of the agents, especially the alcohols and volatile organic solvents, share some of the physical properties and biological actions of ethanol, which is notorious for the Fetal Alcohol Syndrome and Fetal Alcohol Effects that result following prenatal exposures. Limited suggestive clinical evidence points to potentially similar outcomes following solvent exposures. This R21 Exploratory and Developmental Research proposal is designed as a first step to investigate neurobehavioral effects in offspring following developmental exposures to inhalant-abused solvents. Toluene will be used in these initial studies since it is found in many of the mixtures abused via inhalation. Different groups of pregnant rats, and then the dams with their offspring, will be exposed for 10 or 30 minutes to a high concentration of toluene (10,000 ppm maximum). Functional assessments in the offspring will include four procedures: (1) The hindlimb splay response assesses peripheral neuropathy. (2) General motor activity provides an index of the joint outcome of several functional capacities. (3) The acoustic startle response (ASR) measures sensory-motor reactivity. (4) Schedule-controlled operant behavior assesses learning. A demonstration of functional impairment produced by such developmental exposures will serve as the basis for a more extensive proposal designed to address critical questions about the roles of exposure variables, critical periods of development, and different solvents, among others.
