Critical goal of drug addiction research is to understand the differences between recreational and compulsive drug use, the latter being diagnostic of addiction. The dopamine (DA) transmission in the nucleus accumbens (NAc) is an obvious starting point in the search for neuroadaptations responsible for the addictive process. However, despite the evidence for the role of DA uptake in the acute reinforcing and psycho-stimulant effects of cocaine, it remains to be determined whether changes in the physiology of the DA system account for the development of addiction. The proposed studies in this application will bring together state-of-the-art neurochemical techniques (fast scan cyclic voltammetry and microdialysis) learned during the applicant's graduate and post-doctoral training with newly developed behavioral approaches that help identify changes in the motivation of animals to self-administer cocaine. The following questions will be answered over the course of the award: 1. What are the consequences of a cocaine self-administration procedure, which produces an increase in the reinforcing effect, on DA dynamics in the nucleus accumbens. 2. What changes occur in DA receptor and DA transporter levels in the ventral tegmental area, caudate putamen and nucleus accumbens following cocaine self-administration. 3. What is the relationship of fast DA signaling (sub-second DA transients) in the nucleus accumbens with increased motivation to self-administer cocaine. The benefits of this research plan are twofold. First, the Candidate will receive excellent mentored training both in state-of-the-art behavioral techniques and in areas of in vitro receptor pharmacology. Second, unprecedented information on DA neurotransmission will be gathered. Specifically, tonic and phasic DA release, DA uptake and DA receptor modulation will be measured in nucleus accumbens core and shell during and after cocaine self-administration. An improved understanding of the relationship between brain chemistry and drug motivated behavior should provide insights that will lead to the development of better prevention and treatment strategies.
| Bass, Caroline E; Grinevich, Valentina P; Kulikova, Alexandra D et al. (2013) Terminal effects of optogenetic stimulation on dopamine dynamics in rat striatum. J Neurosci Methods 214:149-55 |
| Pattison, Lindsey P; McIntosh, Scot; Budygin, Evgeny A et al. (2012) Differential regulation of accumbal dopamine transmission in rats following cocaine, heroin and speedball self-administration. J Neurochem 122:138-46 |
| Budygin, E A; Park, J; Bass, C E et al. (2012) Aversive stimulus differentially triggers subsecond dopamine release in reward regions. Neuroscience 201:331-7 |
| van Zessen, Ruud; Phillips, Jana L; Budygin, Evgeny A et al. (2012) Activation of VTA GABA neurons disrupts reward consumption. Neuron 73:1184-94 |
| Pattison, Lindsey P; Bonin, Keith D; Hemby, Scott E et al. (2011) Speedball induced changes in electrically stimulated dopamine overflow in rat nucleus accumbens. Neuropharmacology 60:312-7 |
| Bass, Caroline E; Grinevich, Valentina P; Vance, Zachary B et al. (2010) Optogenetic control of striatal dopamine release in rats. J Neurochem 114:1344-52 |
| Oleson, Erik B; Talluri, Sanjay; Childers, Steven R et al. (2009) Dopamine uptake changes associated with cocaine self-administration. Neuropsychopharmacology 34:1174-84 |
| Oleson, Erik B; Salek, Jonathan; Bonin, Keith D et al. (2009) Real-time voltammetric detection of cocaine-induced dopamine changes in the striatum of freely moving mice. Neurosci Lett 467:144-6 |
| Mathews, Tiffany A; Brookshire, Bethany R; Budygin, Evgeny A et al. (2009) Ethanol-induced hyperactivity is associated with hypodopaminergia in the 22-TNJ ENU-mutated mouse. Alcohol 43:421-31 |
| Anstrom, K K; Miczek, K A; Budygin, E A (2009) Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience 161:3-12 |
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