Alcohol use disorder is a serious public health concern, yet its cause remains elusive; we still do not fully understand the neurophysiological mechanisms that drive EtOH consumption. All addictive drugs activate dopamine (DA) neurons, and this was assumed to only cause a synaptic increase of the neurotransmitter DA. However, recent evidence suggests that DA neurons also release the inhibitory neurotransmitter GABA, which equips DA neurons with another level of control over the striatum. Using transgenic mice, viral manipulations, and EtOH drinking behavior, the experiments proposed here will provide a mechanistic account of the role of GABA co-release from DA neurons in EtOH consumption. The results will also provide another level of mechanism ? using two-photon imaging, optogenetics, and electrophysiology, the post-synaptic consequences of DA and GABA co-release on dendritic excitability will be defined. The mechanistic insight gained from these studies could inform novel treatment strategies for alcohol use disorder.

Public Health Relevance

About 70 million American have struggled with alcohol use disorder (AUD) at some point in their lives. However, there are only 3 FDA approved treatments, one of which was developed almost 100 years ago. Using state of the art techniques in neuroscience, this research will explore how a gene linked to AUD leads to enhanced ethanol consumption and will provide strategies to reverse the propensity for excessive drinking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AA027432-02
Application #
9868806
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Cui, Changhai
Project Start
2019-03-01
Project End
2022-02-28
Budget Start
2020-03-01
Budget End
2021-02-28
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stanford University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305