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REGULATION OF DOPAMINE TERMINAL RELEASE IN THE NUCLEUS ACCUMBENS: IMPLICATIONS FOR ALCOHOL ADDICTION

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abstract
Alcoholism and drug addiction are both characterized by continued substance abuse despite adverse consequences. Dopamine signaling in the nucleus accumbens is thought to encode reward and reinforcement, and aberrations in dopamine signaling are suggested to mediate some of the maladaptive motivational behaviors associated with addiction. Measuring dopamine signaling in nucleus accumbens slices with fast scan cyclic voltammetry allows for pharmacological assessment of dopamine terminal release regulation and has provided a wealth of information regarding how drugs of abuse affect dopamine terminal function. However, this experimental approach traditionally requires local electrical stimulation of the tissue in order to induce dopamine release, and electrical stimulation activates local endogenous microcircuits that modulate dopamine release through a variety of heteroreceptors located on dopamine terminals. Ethanol effects on mesolimbic dopamine signaling are varied and complex, and likely involve both direct and indirect actions on dopamine neurons. Here we employed optogenetics in order to selectively stimulate dopamine terminals in nucleus accumbens slices. This method allowed us to measure stimulated dopamine release in response to acute ethanol insult and following chronic ethanol exposure in order to better understand the direct effects of ethanol on dopamine terminals. We used this information to speculate on how ethanol and dopamine interactions in the nucleus accumbens may contribute to the development of alcohol use disorders.
subject
Dopamine
Ethanol
Nucleus Accumbens
Optogenetics
Voltammetry
contributor
Melchior, James Ryland (author)
Jones, Sara (committee chair)
Milligan, Carol (committee member)
Jones, Sara (committee member)
McCool, Brian (committee member)
Weiner, Jeff (committee member)
Espana, Rodrigo (committee member)
date
2017-08-22T08:35:24Z (accessioned)
2017-08-22T08:35:24Z (available)
2017 (issued)
degree
Physiology and Pharmacology (discipline)
identifier
http://hdl.handle.net/10339/86343 (uri)
language
en (iso)
publisher
Wake Forest University
title
REGULATION OF DOPAMINE TERMINAL RELEASE IN THE NUCLEUS ACCUMBENS: IMPLICATIONS FOR ALCOHOL ADDICTION
type
Dissertation

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