(provided by candidate): My immediate short-term goal is to obtain a tenure-track faculty position at a Ph.D. granting university. My long-term goal is to lead a neurochemistry research group focusing on the neuroadapations produced by long-term exposure to alcohol. In order to understand the neuroadaptions produced by alcoholism, my laboratory will use two biosensor techniques in vivo microdialysis and in vitro voltammetry to evaluate the neurotransmitter dopamine. Approximately, 20 million people within the United States endure alcohol abuse, which leads to about $200 billion dollars lost per year. This proposal has two aims (1) to understand the interaction between brain derived neurotrophic factor (BDNF) and dopamine in the brain by using mice that have a 50% reduction in BDNF levels (BDNF) and (2) to evaluate the effects of chronic alcohol exposure on the dopamine system in control and BDNF. The ultimate objective is to determine if an imbalance between BDNF and dopamine may lead to abuse of alcohol or protect the brain from expressing biochemical adaptions associated with the addiction process. Most drugs of abuse;like ethanol, have the ability to elevate extracellular dopamine levels in brain areas such as the caudate-putamen and nucleus accumbens. This dopamine release is thought to play an important role in the stimulant properties of drugs of abuse. Recent evidence shows that BDNF is able to modulate dopamine neurotransmission, but the most direct evidence illustrates BDNF's control over the dopamine D3 receptor. Using in vivo microdialysis, extracellular dopamine levels will be evaluated in the presence or absence of dopamine D3 receptor agonist in control and BDNF mice. Next, in vitro voltammetry experiments will examine the effect of reduced levels of BDNF on dopamine release, uptake and the dopamine D3 receptor. We hypothesize BDNF mice will have low BDNF levels and a low functioning dopamine system, resulting in a tendency to drink greater amounts of alcohol. The second goal is to evaluate the dopamine system in BDNF and control mice three days after a chronic alcohol regiment. We hypothesize that chronic ethanol will decrease endogenous BDNF and DA levels. Using the in vivo microdialysis and in vitro voltammetry we will characterize the dopamine system following 3 days of ethanol withdrawal. The impact of this research is to improve our knowledge of the molecular mechanism of alcohol abuse in an effort to develop better treatments and/or therapeutics.
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|Apawu, Aaron K; Maina, Francis K; Taylor, James R et al. (2013) Probing the ability of presynaptic tyrosine kinase receptors to regulate striatal dopamine dynamics. ACS Chem Neurosci 4:895-904|
|Maina, Francis K; Khalid, Madiha; Apawu, Aaron K et al. (2012) Presynaptic dopamine dynamics in striatal brain slices with fast-scan cyclic voltammetry. J Vis Exp :|
|Bosse, Kelly E; Maina, Francis K; Birbeck, Johnna A et al. (2012) Aberrant striatal dopamine transmitter dynamics in brain-derived neurotrophic factor-deficient mice. J Neurochem 120:385-95|
|Bosse, Kelly E; Mathews, Tiffany A (2011) Ethanol-induced increases in extracellular dopamine are blunted in brain-derived neurotrophic factor heterozygous mice. Neurosci Lett 489:172-6|
|Maina, Francis K; Mathews, Tiffany A (2010) A functional fast scan cyclic voltammetry assay to characterize dopamine D2 and D3 autoreceptors in the mouse striatum. ACS Chem Neurosci 1:450-462|