The identification of neurobehavioral effects which may be induced in animals by environmental compounds is at present hindered by two major factors. First, since the central nervous system (CNS) contains redundant mechanisms and the ability to compensate for focal neuronal damage, often chemicals that may subtly affect the integrity of the CNS may have their actions go undetected by conventional behavioral measures. Second, there are at present few established animal models which relate specific undesirable neuronal changes to chemically induced behavioral changes. The long-term goals of this project are to identify how systematic exposure to uncontrollable stress may unmask subtle behavioral effects resulting from low-level exposure to environmental compounds. These effects will be studied using the general experimental procedures of an animal model of stress induced behavioral deficits and neurochemical change that has received validation as an animal model of human depression. To accomplish this aim, three halogenated aromatic hydrocarbon compounds (dieldrin, chlordecone, polybrominated biphenyls) whose known actions in the CNS make them good candidates for study will be evaluated for behavioral effects in animals exposed to uncontrollable stress, controllable stress or no stress. Chemical exposure will include acute and sub-chronic treatment. Behavioral effects will be assessed as the degree to which the stress/chemical pretreatment modifies the experimental subject's ability to perform a subsequent shock- escape task. Following behavioral testing, regional brain levels will be determined of those neurotransmitters (catecolamines, serotonin and their metabolites) where significant changes have previously been reported for stress alone. it is hypothesized that low-level exposure to these compounds will potentiate those behavioral and neurochemical changes produced by the stress treatment.
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