Despite the evidence for the involvement of dopamine neurotransmission in the acute reinforcing and stimulating effects of alcohol, the role of dopamine release in alcohol drinking behavior is poorly understood. Proposed experiments will determine if initial measures of accumbal dopamine signaling are associated with increased ethanol-drinking or rather if adaptive changes in dopaminergic transmission, associated with the acquisition of operant ethanol-self administration, are most predictive of ethanol drinking measures. Moreover, we will employ optogenetic approaches to test the causal role of specific dopamine release patterns in regulating appetitive and consummatory drinking behaviors and to determine how glutamatergic projections from the basolateral amygdala and prefrontal cortex influence accumbal dopamine signaling and operant ethanol self-administration. At the conclusion of this project, we will have identified dopamine release patterns and brain regions, which increase or inhibit alcoho consumption. This functional mapping of the microcircuitry contributing to alcohol consumption will be critical for the developing effective treatment strategy for alcohol abuse.
The proposed work will bring together behavioral and neurochemical techniques along with genetic and optical approaches to address issues related to neurobiological mechanisms of alcohol addiction. The results of this study may potentially lead to new therapeutic strategies to dampen interest in alcohol drinking.
|Mikhailova, Maria A; Bass, Caroline E; Grinevich, Valentina P et al. (2016) Optogenetically-induced tonic dopamine release from VTA-nucleus accumbens projections inhibits reward consummatory behaviors. Neuroscience 333:54-64|
|Efimova, Evgeniya V; Gainetdinov, Raul R; Budygin, Evgeny A et al. (2016) Dopamine transporter mutant animals: a translational perspective. J Neurogenet 30:5-15|
|Fox, Megan E; Mikhailova, Maria A; Bass, Caroline E et al. (2016) Cross-hemispheric dopamine projections have functional significance. Proc Natl Acad Sci U S A 113:6985-90|
|Budygin, E A; Weiner, J L (2015) Exploring the Neurochemical Basis of Alcohol Addiction-Related Behaviors: Translational Research. Transl Biomed 6:|
|Adamah-Biassi, Ekue B; Almonte, Antoine G; Blagovechtchenski, Evgeny et al. (2015) Real time adenosine fluctuations detected with fast-scan cyclic voltammetry in the rat striatum and motor cortex. J Neurosci Methods 256:56-62|
|Park, Jinwoo; Bucher, Elizabeth S; Budygin, Evgeny A et al. (2015) Norepinephrine and dopamine transmission in 2 limbic regions differentially respond to acute noxious stimulation. Pain 156:318-27|