The main objective of this project is to obtain an understanding of the possible interaction between ethanol and changing hormonal environments and what effect this has on the developing brain, especially the cerebellum. A secondary objective is to define parameters which will allow for a direct correlation of findings on ethanol effects in the developing brains of amphibians and rodents in an effort to aid our search for basic biological principles rather than species specific effects in fetal alcohol syndrome studies. We propose experiments which are expected to provide information on the effect of ethanol on the developing cerebellum during all three trimester equivalent periods, a developmental time during which the hormonal environment changes from a high prolactin to a high thyroxine level, and during which time the cerebellum undergoes all stages of development; from initial differentiation of the cerebellar anlage to maturation of its constituent cells. Other experiments will examine the differential effect of continuous versus episodic periods of ethanol exposure on the developing cerebellum and, finally, experiments will be performed in which the hormonal environment of the developing cerebellum will be altered by the administration of exogenous hormones or anti-hormonal agents and the effect of ethanol will be studied in these modified hormonal environments. The proposed studies will use light microscopic, autoradiographic and immunocytochemical methods at both qualitative and quantitative levels. The frog tadpole will be the animal used in these experiments since it is an unusually well suited animal model for these particular studies. This is due to several factors including the very long developmental stage which lasts 2-3 years and that the tadpole is a free swimming embryo whose hormonal environment is not affected by its mother and can be manipulated readily. Insights into interactions between ethanol and hormones which are known to affect brain development will aid our efforts to understand the varied and sometimes subtle effects of ethanol on the developing brain and its manifestation in the fetal alcohol syndrome, which varies from gross malformation to mental retardation.
