Rapid dopamine dynamics after repeated cocaine exposure

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DESCRIPTION (provided by applicant): Cocaine abuse in the United States continues to be of concern with an estimated 1 million new cocaine users each year (USHHS, 2006). Cocaine acts to inhibit dopamine transporters in the brain, which in turn increases dopamine availability to produce feelings of euphoria. In addition, these dopamine effects lead to several behavioral changes including locomotor hyperactivity, cocaine seeking behavior and cocaine self- administration. While the microdialysis literature has illustrated a progressive, or sensitized, increase in dopamine levels and locomotor hyperactivity with repeated cocaine exposure, these studies have not been extended to include rapid dopamine dynamics. Fast scan cyclic voltammetry (FSCV), which can detect dopamine fluctuations on a sub-second time scale, provides an ideal means for such analyses. Further, an understanding of these rapid dopamine dynamics is important as they have been observed in response to acute cocaine administration and may play a role in behavioral responses to cocaine. The work proposed here will use in vivo FSCV to 1) characterize real time dopamine release in the nucleus accumbens core and shell after acute and repeated cocaine exposure and 2) determine the role of rapid dopamine release in the nucleus accumbens in cocaine-mediated locomotor sensitization. Specifically, in vivo FSCV recordings will be performed in rats after different periods of cocaine administration and withdrawal in order to fully characterize these dopaminergic responses. ' r The overall goal of this research is to determine how long term cocaine exposure alters dopamine effects in the brain to infleunce behavior. Such work will provide valuable insight as to how such processes may contribute to cocaine abuse in humans.