Defining the role of neuroimmune interactions in ethanol effects on ventral tegmental area GABA neurons and nucleus accumbens dopamine release 4189

Abstract Description Alcohol use disorder (AUD) is a common medical condition characterized by an impaired ability to stop or control alcohol use. Approximately 28.1 million adults and 757,000 adolescents had AUD in the past year, indicating a public health crisis within the US. The prevailing dogma in the alcohol field is that the rewarding properties of ethanol (EtOH) result from enhancement of ventral tegmental area (VTA) dopamine (DA) neural activity and accompanying DA release in the mesolimbic reward system. Additionally, VTA GABA neurons are inhibited by EtOH in vivo at reinforcing doses. However, VTA DA and GABA neurons in brain slices are insensitive to EtOH indicating that EtOH effects in vivo appear to involve upstream targets. We have shown that EtOH enhances blood DA levels and leukocyte DA D2 receptor (D2R) expression, and depletion of monocytes/macrophages disrupts EtOH effects on VTA GABA firing and DA release. This data suggests a neuroimmune interaction for EtOH use and challenges theories of exclusively central effects of EtOH on DA neuronal activity. Little is known about how local and peripheral immune cells signal to mesolimbic circuits. We have identified cytokines that are upregulated and downregulated upon EtOH exposure and are characterizing their effects on dopamine production. This data will provide new, fundamental knowledge on the neurobiology of EtOH reward and dependence and the role of peripheral substrates that may help improve drug development efforts. Funding Sources PHS support provided to JTY (R01 AA030577) Topic Categories Neuroimmunology (NEUR)