Anti-inflammatory drugs reduce ethanol-mediated microglia activation (Qin and Crews, 2012a), and studies directly targeting microglia in alcohol behaviors are now in the early stages (Table 5). Pharmacological depletion of microglia (with colony-stimulating factor-1 receptor antagonist, PLX3397) blunts the induction of TNF-α and the enhanced expression of anti-inflammatory genes, IL-4 and IL-10, that occur following acute withdrawal from binge ethanol drinking, indicating that microglia are at least partly necessary for the brain’s pro-inflammatory response to ethanol (Walter and Crews, 2017). However, unlike a previous report using minocycline to inhibit activation (Yue Wu et al., 2011), microglia depletion with PLX3397 does not alter ethanol-induced motor impairment (Walter and Crews, 2017). Although the effects of microglial depletion on alcohol drinking behaviors are unknown, using minocycline to inhibit activation decreases ethanol self-administration in mice (Agrawal et al., 2011; Lainiola and Linden, 2017) and attenuates ethanol withdrawal-induced anxiety and relapse drinking following ethanol deprivation in rats (Gajbhiye et al., 2018). Another study found that minocycline does not affect withdrawal-induced anxiety (Harper et al., 2018), perhaps due to differences in length of ethanol exposure and anxiety measurements.
