The mechanisms that underlie the development of ethanol reinforcement are not fully understood, but the involvement of dopamine in the mesocorticolimbic system has been hypothesized for some time. It is clear that ethanol administration stimulates dopamine release in this system, but the role of dopamine during various phases of the development of ethanol reinforcement is unclear. Studies done in the last grant period show that dopamine activity undergoes plasticity during the development of the reinforcing properties of ethanol such that a transient increase in accumbal dopamine occurs during consumption of ethanol after a few days of exposure to ethanol, but not during an initial exposure. This transient increase in dopamine is correlated with exposure to the stimulus properties of ethanol rather than the brain concentration of ethanol. Recent work has implicated the role of subregions of the nucleus accumbens (core and shell) as having different functional roles in natural and drug reward. Also, the prefrontal cortex is known to be involved in motivated behavior such as drug seeking behavior. Therefore, we hypothesize that the development of ethanol reinforcement is mediated by the enhancement of dopamine activity in these various brain areas at various times during the development ethanol reinforcement.
The specific aims of the proposal are to determine (1) the effect of ethanol consumption on dopamine release in vivo in the prefrontal cortex and nucleus accumbens (core and shell) of Long Evans rats at early phases in the development of reinforcement, (2) the effects of ethanol through i.v. administration on extracellular dopamine in the mesocorticolimbic system during an initial exposure to ethanol in the drinking solution, and (3) whether the taste and smell of ethanol contribute to the transient dopamine response observed during oral ethanol consumption. Together the experiments proposed will provide new data on the role of dopamine in the early stages of the development of ethanol reinforcement in a behaviorally relevant context.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA011852-06
Application #
6936046
Study Section
Neurotoxicology and Alcohol Study Section (NAL)
Program Officer
Egli, Mark
Project Start
2000-04-01
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
6
Fiscal Year
2005
Total Cost
$231,027
Indirect Cost
Name
University of Texas Austin
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Thakore, Neha; Reno, James M; Gonzales, Rueben A et al. (2016) Alcohol enhances unprovoked 22-28 kHz USVs and suppresses USV mean frequency in High Alcohol Drinking (HAD-1) male rats. Behav Brain Res 302:228-36
Vena, Ashley A; Mangieri, Regina; Gonzales, Rueben A (2016) Regional Analysis of the Pharmacological Effects of Acute Ethanol on Extracellular Striatal Dopamine Activity. Alcohol Clin Exp Res 40:2528-2536
Reno, James M; Thakore, Neha; Gonzales, Rueben et al. (2015) Alcohol-preferring P rats emit spontaneous 22-28 kHz ultrasonic vocalizations that are altered by acute and chronic alcohol experience. Alcohol Clin Exp Res 39:843-52
Barker, Jacqueline M; Corbit, Laura H; Robinson, Donita L et al. (2015) Corticostriatal circuitry and habitual ethanol seeking. Alcohol 49:817-24
Schier, Christina J; Dilly, Geoffrey A; Gonzales, Rueben A (2013) Intravenous ethanol increases extracellular dopamine in the medial prefrontal cortex of the Long-Evans rat. Alcohol Clin Exp Res 37:740-7
Valenta, John P; Job, Martin O; Mangieri, Regina A et al. (2013) ?-opioid receptors in the stimulation of mesolimbic dopamine activity by ethanol and morphine in Long-Evans rats: a delayed effect of ethanol. Psychopharmacology (Berl) 228:389-400
Schier, Christina J; Mangieri, Regina A; Dilly, Geoffrey A et al. (2012) Microdialysis of ethanol during operant ethanol self-administration and ethanol determination by gas chromatography. J Vis Exp :
Carrillo, Jennifer; Gonzales, Rueben A (2011) A single exposure to voluntary ethanol self-administration produces adaptations in ethanol consumption and accumbal dopamine signaling. Alcohol 45:559-66
Howard, Elaina C; Schier, Christina J; Wetzel, Jeremy S et al. (2009) The dopamine response in the nucleus accumbens core-shell border differs from that in the core and shell during operant ethanol self-administration. Alcohol Clin Exp Res 33:1355-65
Robinson, Donita L; Howard, Elaina C; McConnell, Scott et al. (2009) Disparity between tonic and phasic ethanol-induced dopamine increases in the nucleus accumbens of rats. Alcohol Clin Exp Res 33:1187-96

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