As we discussed for alcohol action, other TLRs and immune receptors are likely important for opioid- and stimulant-induced neuroimmune alterations. For example, morphine-induced microglia activation and pro-inflammatory cytokine expression require TLR2 expression, and TLR2 KO mice show attenuated morphine withdrawal symptoms (Zhang et al., 2011). TLR2 is also implicated in cocaine-induced microglial activation in BV2 cells (Liao et al., 2016). Furthermore, TLR3 deficiency or intra-NAc injection of TLR3 inhibitors significantly attenuates cocaine-induced CPP (Zhu et al., 2018). Recent interest has centered around microglial P2X7R activation as a potential neuroimmune target for addictive behaviors, based on its role in methamphetamine-induced microglia activation (Fernandes et al., 2016) and tolerance to morphine’s analgesic effects (Leduc-Pessah et al., 2017).
