This is an ADAMHA RSDA Level II research proposal. The primary objective of this proposal is to examine the effects of fetal alcohol exposure on the neuroendocrine regulation of reproduction of adult female rats. A secondary objective for this proposal is to provide the principal investigator an extended period of time in which to investigate, in depth, a research project which has issued from prior experimental studies related to investigation of the effects of fetal alcohol exposure on brain differentiation and subsequent neuroendocrinological function. The proposed research project will investigate the effects of fetal and neonatal ethanol exposure on the preoptic and hypothalamic areas involved with regulation of ovulation. Extensive experimental studies will be performed to focus upon the effect of in utero ethanol exposure on the hypothalamic content of luteinizing hormone releasing hormone (LHRH) and the regulation of LHRH during the proestrus period by catecholaminergic content and turnover. The effects of fetal ethanol exposure on steroid feedback inhibition of hypothalamic LHRH will be determined by the examination of hypothalamic estrogen binding and hypothalamic neurotransmitter content and turnover in response to gonadal steroids. Pregnant rats will be fed either a laboratory chow diet ad libitum, a liquid diet containing ethanol (5% v/v), or a liquid diet in which maltose-dextrins have been isocalorically substituted for ethanol. Radioimmunoassay of gonadotrophis in the pituitary gland and serum, and LHRH in the preoptic area and hypothalamus will be made. High pressure liquid chromatography (HPLC) with electrochemical detection will be used for measuring catecholamine content and turnover. Steroid cytosolic binding will be determined by using radioligand binding techniques. The investigation will provide useful basic information regarding the permanent effects of fetal alcohol exposure on the neuroendocrine regulation of reproduction. This grant will allow the principal investigator the uninterrupted time and resources for detailed focus on the research project. Furthermore, it would aid in the development of the career of the P.I. by providing an intensive exposure in the fetal alcohol field of research, and in the general area examining the deleterious effects of ethanol on the central nervous system.
| Robinson, J E; Heaton, R K; O'Malley, S S (1999) Neuropsychological functioning in cocaine abusers with and without alcohol dependence. J Int Neuropsychol Soc 5:10-9 |
