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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA009850-01A1
Application #
2046134
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1994-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Taylor, Anna N; Tio, Delia L; Bando, Jennifer K et al. (2006) Differential effects of alcohol consumption and withdrawal on circadian temperature and activity rhythms in Sprague-Dawley, Lewis, and Fischer male and female rats. Alcohol Clin Exp Res 30:438-47
Taylor, Anna N; Tio, Delia L; Romeo, Horacio E (2005) The febrile response to intraperitoneal lipopolysaccharide: strain and gender differences in rats. J Neuroimmunol 158:86-93
Romeo, Horacio E; Tio, Delia L; Taylor, Anna N (2003) Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation. J Neuroimmunol 136:104-11
Taylor, Anna N; Romeo, Horacio E; Beylin, Anna V et al. (2002) Alcohol consumption in traumatic brain injury: attenuation of TBI-induced hyperthermia and neurocognitive deficits. J Neurotrauma 19:1597-608
Taylor, Anna N; Tio, Delia L; Heng, Ngy S et al. (2002) Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1 beta in male rats. Alcohol Clin Exp Res 26:44-52
Taylor, Anna N; Tritt, Susan H; Tio, Delia L et al. (2002) Maternal adrenalectomy abrogates the effect of fetal alcohol exposure on the interleukin-1beta-induced febrile response: gender differences. Neuroendocrinology 76:185-92
Romeo, H E; Tio, D L; Rahman, S U et al. (2001) The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 115:91-100
Hodgson, D M; Yirmiya, R; Taylor, A N (2001) Intracerebroventricular interleukin-1beta impairs clearance of tumor cells from the lungs: role of brain prostaglandins. J Neuroimmunol 119:57-63
Hodgson, D M; Taylor, A N; Zhang, Z et al. (1999) Lysosphingomyelin prevents behavioral aberrations and hippocampal neuron loss induced by the metabotropic glutamate receptor agonist quisqualate. Prog Neuropsychopharmacol Biol Psychiatry 23:877-92
Hodgson, D M; Yirmiya, R; Chiappelli, F et al. (1999) Intracerebral interleukin-1beta impairs response to tumor invasion: involvement of adrenal catecholamines. Brain Res 816:200-8

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