Ethanol Sensitization in Mice

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The rewarding, hyperlocomotive and addictive properties of drugs of abuse are often associated with an elevation in extracellular dopamine (DA) levels. Locomotor stimulating doses of ethanol produce activation of DA cell bodies in the ventral tegmental area, which leads to increased extracellular DA levels in the terminal fields, such as the striatum and nucleus accumbens. Sensitization refers to an augmented locomotor stimulation produced by repeated ethanol injections. It has been assumed that increases in extracellular DA levels occur in parallel with locomotor sensitization to ethanol. But in fact, there is no literature documenting changes in extracellular DA levels after ethanol sensitization. Understanding the DA neurochemistry behind ethanol sensitization is important because the process of behavioral sensitization has been suggested to contribute to the development of addiction. The goal of this research is to evaluate DA dynamics in the nucleus accumbens of C57BI/6J mice at several time intervals after sensitization. Specifically, microdialysis in freely moving mice and voltammetry in brain slices will be employed to examine the function of the DA system in detail. We postulate that DA and locomotor parameters will sensitize in parallel.