Astrocytes and alcohol: cortical astrocytes regulate alcohol consumption and intoxication

Drug addiction is a complex psychiatric disorder [1]. Most clinical and preclinical research to date focuses on neuronal adaptations following drug use that drive and sustain alcohol use [1, 2]. However, recent studies suggest that glia and glia–neuron interactions may contribute to the development of alcohol use disorder [3, 4]. For example, Erickson et al. reported that sustained alcohol exposure reduces the expression of genes related to G protein-coupled receptor (GPCR) signaling and calcium regulation in mouse prefrontal cortical (PFC) astrocytes [4]. In astrocytes, activation of G_q-coupled GPCRs (G_qGPCRs) leads to elevations in intracellular calcium and to the release of gliotransmitters, such as adenosine triphosphate (ATP), which in turn regulate synaptic transmission [5]. Astrocytic calcium modulation and downstream signaling are linked with multiple behaviors, including attention, cognition, emotional, and motor behaviors, sensory processing, circadian cycling, and drug seeking [3, 5, 6]. Since alcohol exposure produces molecular adaptations in astrocytes [3, 4], it is important to understand whether, and if so, how these changes contribute to alcohol-related behaviors.

In this issue of Neuropsychopharmacology, Erickson et al. examined the potential role of cortical astrocyte calcium signaling in alcohol consumption and intoxication [7]. By utilizing elegant approaches in mice to activate or inhibit calcium signaling in PFC astrocytes, the authors report that chemogenetically stimulating astrocyte-specific calcium signaling increases alcohol consumption and preference, while reducing calcium signaling in PFC astrocytes by overexpressing an exogenous calcium extruding transporter [8] suppresses alcohol consumption and alcohol-induced c-Fos expression.

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