cocaine-induced dopamine release. In addition, (+)-naloxone does not reduce methamphetamine craving during withdrawal (Theberge et al., 2013). Similar to findings from alcohol studies, TLR4 may mediate some components of addiction to opioids and psychostimulants but may not be a primary neuroimmune target. Future studies may benefit from newer tools to target TLR4 in brain, such as LPS from Rhodobacter sphaeroides (LPS-RS), a potent antagonist of LPS-TLR4 signaling (Brown et al., 2017). When injected into the VTA, LPS-RS decreases maintenance but not acquisition of CPP to morphine and cocaine-primed reinstatement of cocaine seeking (Chen et al., 2017b) (Brown et al., 2017). Also, intra-NAc injection of the weak TLR4 agonist, monophosphoryl lipid A, reduces acute behavioral sensitization to cocaine after prolonged abstinence (Lewitus et al., 2016).
