NEUROHUMORAL AND PRENATAL DETERMINANTS OF ALCOHOL INTAKE

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The long-term goal of this project is to understand the mechanisms subserving and/or predisposing to addiction to alcohol and the ways in which such mechanisms are altered by prenatal exposure to alcohol. Using a model of ethanol intake and preference in rats, the effects of administering ethanol (17.5% or 35% ethanol derived calories) in utero (from Day 6 to Day 15 or 20 of gestation) will be investigated pair-fed yoked animals will be included to control for potential nutritional effects. Ethanol intake and preference of rats will be determined at three different postnatal ages. The possibility that endogenous sex steroids may modulate the effects of prenatal ethanol exposure on postnatal ethanol intake will be examined by considering the role of fetal position and in utero contiguity to siblings of the same or opposite sex. The effects of prenatal ethanol exposure on neurotransmitter release in discrete brain regions of developing rats will be determined with the use of in vivo microdialysis. Dopamine, norepinephrine and serotonin release will be measured in nucleus accumbens, striatum and medial prefrontal cortex of awake and freely moving animals; motor behavior will be measured concomitantly and the effects of acute doses of ethanol will also be determined. Lastly, the temporal relationship between ethanol consumption and neurotransmitter release in brain will be studied; in vivo microdialysis will be conducted concurrently with measurement of ethanol intake. An important goal will be to distinguish which neurochemical events precede or elicit ethanol intake and which neurochemical events are the result or consequence of ethanol intake; subsequent studies will examine how these relationships are altered by prenatal ethanol exposure. The results of the work proposed in this project should elucidate the determinants of alcohol intake, the mechanisms involved, and by doing so,, lead to the development of appropriate interventions that could be used to prevent and/or treat alcohol addiction.