Characterizing Molecular Responses to Astrocyte-Specific Excitatory DREADD Activation and Calcium Extruder Expression in Relation to Alcohol Use Disorder
An estimated 15 million people in the United States suffer from Alcohol Use Disorder (AUD), and current pharmacological treatment is not very effective. A goal of AUD research is to understand neuroadaptations that occur in response to alcohol consumption, and to identify molecular targets for potential new treatments. Most AUD and other brain disease research has focused on neuronal mechanisms, but there is increasing interest in the role of glial cells in these disease states.
Astrocyte-specific DREADD activation of Gq-GPCR signaling has been shown to increase alcohol consumption in rodents as well as change the sensitivity to specific alcohol-related behaviors. Investigating the impact of DREADD activation and alcohol exposure on neuronal and astrocytic function would provide insight into the mechanism behind astrocyte DREADD regulation of behavior. The mechanisms underlying the behavioral effects of astrocyte calcium manipulation are still unknown, and it is currently unclear how astrocyte calcium signaling in the PFC affects neuronal activity at baseline levels and in response to ethanol exposure.
We provide early promising results of the cell and molecular responses to astrocyte-specific calcium manipulation to be followed up on. There was little effect on neuronal activity in the PFC by astrocyte-specific DREADD activation or the expression of an astrocyte-specific calcium extruder protein. However, we found that astrocyte calcium activation may interact with neuronal responses to alcohol exposure in the PFC. Finally, based on established pathways between the PFC and NAc brain regions, this research points to astrocyte-specific DREADD activation in the PFC affecting neuronal activity in the NAc.