(Bull et al., 2015). In the NAc, GFAP immunoreactivity increases after 3 weeks of abstinence following chronic intermittent ethanol self-administration and is positively correlated with motivation to resume self-administration following abstinence (Bull et al., 2014). Sex is also a factor in astrocyte reactivity, as female mice exhibit greater increases in GFAP in response to chronic alcohol treatment compared with males (Alfonso-Loeches et al., 2013). Results from human postmortem alcoholic brain are varied, showing either increased GFAP in PFC (Rubio-Araiz et al., 2016), decreased astrocyte density (Miguel-Hidalgo et al., 2002, 2006), or altered astrocyte morphology (Cullen and Halliday, 1994). Anatomical, molecular, and functional differences in astrocytes between species could partially explain varied findings from studies performed in mouse or human tissue (Oberheim et al., 2009, 2012). For example, hominid cortical astrocytes are larger, more complex, and comprised of more subtypes compared to astrocytes in other mammals (Oberheim et al., 2006). More specific human astrocyte markers that account for functional heterogeneity and distinguish distinct activation states are needed to assess possible changes in astrocyte phenotype in response to alcohol. Overall, these studies show that astrocyte function is dynamically regulated by alcohol exposure.
