Ethanol drinking involves astrocytes in male Wistar rats

Astrocytes are the most abundant glial cells in the brain and an integrative component of the neural network. Studies have shown that ethanol altered expression of an astrocyte marker, i.e., glial fibrillary acidic protein (GFAP), in two key corticolimbic regions, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). These regions comprise anatomically and functionally different subregions, i.e., the prelimbic (PL) and infralimbic (IL) cortex of the mPFC, the shell and core subregions of the NAc. However, ethanol effects on GFAP expression within these subregions remain largely unknown. In addition, effects of pharmacological manipulation of astrocytes on alcohol drinking have been understudied. Western blot was conducted to determine GFAP expression in subregions of the mPFC and NAc after chronic intermittent ethanol drinking. Fluorocitrate, a preferential metabolic inhibitor of astrocytes, was tested on intermittent ethanol drinking following administration into the lateral ventricle. Chronic intermittent ethanol drinking enhanced GFAP protein expression in the PL cortex and NAc core, but not in the IL cortex or NAc shell. Fluorocitrate reduced ethanol intake and preference without altering total fluid consumption. In addition, fluorocitrate did not affect water drinking when water was the only solution or basal locomotor activity. These results indicate that intermittent ethanol drinking induced GFAP elevation in a subregion-specific manner within the mPFC and NAc, and that a preferential metabolic inhibitor of astrocytes selectively attenuated ethanol drinking without non-specific inhibition of water drinking or general activity. Together, these results suggest that astrocytes may play an important role in chronic intermittent ethanol drinking.