Allopregnanolone is a neurosteroid and reduced progesterone metabolite synthesized in the nervous system of vertebrates. Allopregnanolone is an antiepileptic, anxiolytic, mood elevating drug and emerging as a therapeutic choice for neuropsychiatric and neurodegenerative disorders. Allopregnanolone modulates neuronal functions via both nongenomic and genomic mechanisms. However, the genomic effects of allopregnanolone are poorly understood. Allopregnanolone also alters various behavior patterns including learning and memory but the mechanisms involved beyond this largely remain unknown. In amphibian brains, synthesis of various neurosteorids is well established, however the endogenous synthesis of 5 alpha and 5 alpha-3 alpha reduced neurosteroids such as allopregnanolone, THDOC and androstanediol, in amphibian brain is not demonstrated yet. The studies in this project include three main objectives. First, we examined the global genomic effects of allopregnanolone on neuroendocrine circuits using amphibian (Xenoups laevis) brain. Second, we studied the role of allopregnanolone on intracellular signaling mechanisms of synaptic plasticity--a basic conserved cellular mechanism underlying learning and memory formation. Third, we studied the expression and localization patterns of mRNA encoding steroidogenic enzymes that are involved in 5 alpha and 5 alpha-3alpha reduced neurosteroid synthesis in amphibian brain. To study the global genomic effects of allopregnanolone, isolated in vitro brains were treated with micromolar doses of allopregnanolone. Using microarray technology and bioinformatic tools, we identified novel regulatory roles for allopregnanolone on various neuroendocrine and neurotransmitter circuits at the transcript level. Allopregnanolone regulated several critical transcription factors and genes involved in the neuronal cell cycle, differentiation, development, neurite growth, axon guidance, cytoskeletal remodeling, neurodegeneration and inflammatory processes. To identify the potential role of allopregnanolone on intracellular signaling mechanisms of synaptic plasticity, isolated in vitro brains were treated with a wide range of allopregnanolone doses with or without an NMDA receptor blocker. Allopregnanolone regulated the molecular signaling components implicated in cerebellar longterm depression, fear conditioned plasticity and bidirectional synaptic plasticity. As a third project, in situ hybridization and reverse transcription PCR studies demonstrated that expression of mRNA encoding the steroidogenic enzymes srd5a1, srd5a3 and akr1c2 is wide spread across the amphibian brain. The localization patterns of mRNA suggests a possible functional role of 5 alpha and (or) 5 alpha-3 alpha reduced neurosteroids in olfaction, multimodal sensory integration, auditory communication and neuroendocrine systems of amphibians. The expression of mRNA encoding srd5a3 enzyme, a novel isoform of 5 alpha reductase, suggests that it may be involved in the synthesis of 5α DHT in the brain, apart from peripheral androgenic targets.