Dysfunction of neuroendocrine and neurotransmitter activity has been linked to many of the psychological, social and pathophysiological consequences of alcoholism. The long term goal of this project is to determine the effects of alcohol on particular peptide- and catecholamine-containing neuronal systems using the laboratory rat as an experimental animal model for comparison with the same neurosubstances and regions of postmortem brains from human alcoholics. Neuroendocrine cells containing vasopressin (VP), oxytocin (OT), and beta-endorphin (B-E) will be quantified using radioimmunoassay (RIA), while immunonblotassay (IBA) will be used to measure enzymatic activity of tyrosine hydroxylase (TH). Light microscopic (LM-) and electron microscopic immunocytochemistry (EM-ICC) will be utilized to determine numbers of chemically-identified neuronal perikarya and their ultrastructural characteristics in animals administered alcohol vs. controls. The treatment group of rats will be administered either an alcohol or liquid control diet using the simultaneous pair- feeding system, and in the case of the withdrawal group, allowed a recovery period following treatment. The experimental paradigm used for the animal studies will determine the effects of alcohol both on the quantity of neurosubstances in micropunch samples of specific brain regions, and numbers of chemically- identified cell bodies. Similarly, RIA and IBA assays will be done in one-half, while numbers of cell bodies stained with LM-ICC will be counted in the other half of human brains of alcoholics vs. age-matched controls. Since VP, OT, B-E and catecholamines have been shown to play a role in learning and memory, then correlative analysis of results from these studies should elucidate the biochemical and morphological alterations alcohol may have on neuroendocrine and catecholaminergic circuits of the animal and human brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA006014-04A1
Application #
3109240
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1983-05-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Franci, C R; Anselmo-Franci, J A; Kozlowski, G P et al. (1993) Actions of endogenous vasopressin and oxytocin on anterior pituitary hormone secretion. Neuroendocrinology 57:693-9
Kozlowski, G P; Sterzl, I; Nilaver, G (1992) Localization patterns for immunoglobulins and albumins in the brain suggest diverse mechanisms for their transport across the blood-brain barrier (BBB). Prog Brain Res 91:149-54
Kozlowski, G P; Nilaver, G; Zlokovic, B V (1990) Immunoneurology: a serum protein afferent limb to the CNS. Adv Exp Med Biol 274:345-70
Iwamoto, G A; Mitchell, J H; Sadeq, M et al. (1989) Localization of tyrosine hydroxylase and phenylethanolamine N-methyltransferase immunoreactive cells in the medulla of the dog. Neurosci Lett 107:12-8
Dees, W L; Skelley, C W; Rettori, V et al. (1988) Influence of ethanol on growth hormone secretion in adult and prepubertal female rats. Neuroendocrinology 48:495-9
Rettori, V; Skelley, C W; McCann, S M et al. (1987) Detrimental effects of short-term ethanol exposure on reproductive function in the female rat. Biol Reprod 37:1089-96
Dees, W L; Ahmed, C E; Ojeda, S R (1986) Substance P- and vasoactive intestinal peptide-containing fibers reach the ovary by independent routes. Endocrinology 119:638-41
Dees, W L; Kozlowski, G P; Dey, R et al. (1985) Evidence for the existence of substance P in the prepubertal rat ovary. II. Immunocytochemical localization. Biol Reprod 33:471-6
Dees, W L; Rettori, V; Kozlowski, G P et al. (1985) Ethanol and the pulsatile release of luteinizing hormone, follicle stimulating hormone and prolactin in ovariectomized rats. Alcohol 2:641-6
Dees, W L; Skelley, C W; Kozlowski, G P (1985) Central effects of an antagonist and an antiserum to substance P on serum gonadotropin and prolactin secretion. Life Sci 37:1627-31

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