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.
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.
