Fetal alcohol exposure (FAE) is associated with significant long- lasting alterations in neurobiological and -behavioral functions. These alterations are consequential to the effects of FAE on the development of the central and peripheral nervous systems, as well as the neuroendocrine and the immune systems. The interaction between these systems can also modulate behavior. The effects of FAE upon neuroendocrine-immune-behavioral interactions remain to be elucidated. To test the hypothesis that FAE impairs the ontogeny of neuroendocrine-immune-behavioral interactions in rats, we will challenge the immune system of FAE and control (pair-fed and normal) off-spring in vivo with the administration of lipopolysaccharide (LPS). LPS effects on motor activity, spatial learning, analgesic response, body temperature, and hypothalamo-pituitary-adrenal (HPA) activity (plasma ACTH and corticosterone levels) will be assessed in neonatal, peripubertal and adult male and female FAE and control offspring. To begin to study mechanisms for the altered neuroendocrine and behavioral responses, the pattern of cytokine production in plasma and brain (i.e., IL-1, IL-2 TNF) will be monitored following LPS administration. To begin to characterize the prenatal mechanisms responsible for the teratogenic effects of FAE, we will test whether or not adrenalectomy of the dams and supplementation with low dose glucocorticoids effectively prevents the FAE-induced impairment of normal neuroendocrine-behavioral-immune interactions. To exclude the putative role of the dams' catecholaminergic system, parallel experiments with adrenal demodulated dams will be performed. To exclude the putative role of the dams' endogenous opioid system, parallel experiments with dams treated with the opioid antagonist naltrexone will also be performed.
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