Ethanol is abused by millions of Americans every year. Unfortunately, the mechanisms of ethanol reinforcement are not clear. As a result, therapy for alcohol dependence can be quite challenging. One possible therapeutic target is the mesolimbic dopaminergic system. This pathway contains dopaminergic neurons spanning from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc), and is implicated in ethanol reinforcement. However, the exact role of dopamine in ethanol reinforcement is not known. The nucleus accumbens is described as having core and shell subregions, and dopamine in these two areas may play different roles in ethanol reinforcement.
One aim of this proposal is to monitor ethanol evoked dopamine release in the nucleus accumbens core and shell with microdialysis after ethanol selfadministration. These experiments will use microdiaylsis to measure dopamine levels in one of these subregions while a Long-Evans rat is responding for ethanol in an operant paradigm. This will allow comparison of any changes in dopamine between the two regions. Another aim described in this proposal will attempt to uncover the mechanism through which the core and shell are involved in ethanol selfadministration. Previously, viral-expression of dopmaine receptors has been useful in investigating the role of the nucleus accumbens in ethanol administration. However, other laboratories have not separated their manipulations of dopamine receptors into the core and shell subregions of the accumbens. In order to test whether upregulation of dopamine 1 dopamine receptors (D1DRs) are involved in ethanol reinforcement, the D1DR will be upregulated selectively in the core or shell using a sindbis viral vector. Operant ethanol selfadministration behaviors will be measured before and after the upregulation. The results of these studies will increase our understanding of dopamine's role in the reinforcing effects of ethanol, and whether the core and shell subregions play different parts in this process. ? ? Public Health Relevance: The results of this study will provide information about ethanol-evoked dopamine release and the role of the D1DR in ethanol administration. These experiments may clarify whether dopamine plays a role in ethanol reinforcement. A greater understanding of ethanol's effects on the brain is crucial to understanding why so many people are dependent on this drug of abuse. ? ? ?
| 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 |
| 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 |
| Howard, E C; Schier, C J; Wetzel, J S et al. (2008) The shell of the nucleus accumbens has a higher dopamine response compared with the core after non-contingent intravenous ethanol administration. Neuroscience 154:1042-53 |
