Alcohol is often co-abused with illicit drugs (Soyka, 2015; Witkiewitz and Vowles, 2018) that further alter neuroimmune signaling. Opioids and psychostimulants activate brain microglia and increase levels of astrocyte markers, induce chemokines, increase levels of cytokines (e.g., IL-β and TNF-α), and produce neuronal dysfunction (Beitner-Johnson et al., 1993; El-Hage et al., 2006; Fernandes et al., 2016; Frank et al., 2016; Gonçalves et al., 2017; Hutchinson et al., 2011; Lewitus et al., 2016; Lloyd et al., 2017; Sawaya et al., 2009; Schwarz et al., 2011; Taylor et al., 2016). Furthermore, stressful experiences and adolescent pre-exposure to drug use facilitate these neuroimmune responses (Orso et al., 2017; Schwarz and Bilbo, 2013). Combining substances of abuse may have synergistic effects on neuroimmune activation and cognitive deficits, as was observed in rats administered chronic morphine and alcohol (Adedayo et al., 2018). As with alcohol, the drug exposure procedures, brain regions, and time points analyzed are some of the variables that can impact findings. A comprehensive review of the neuroimmune actions of opioids and psychostimulants can be found in (Lacagnina et al., 2017). Although many mechanistic questions remain, some common themes are emerging that may also enlighten alcohol-neuroimmune research.
