Opiates are known to be addicting drugs and have endogenous opiate receptors that contribute to the neurobiology of addiction (Koob and Volkow 2010). Opiate antagonists are used to treat both alcohol and opiate addiction. Interestingly, opiate antagonists block innate immune gene induction through a different novel mechanism that might contribute to the reversal of addiction-like behavior. LPS, endotoxin, induces large innate immune responses that are blocked by opiate antagonists (Liu et al. 2000) and protect dopamine neurons through inhibition of microglial innate immune activation and reduced NOX formation of ROS (Liu et al. 2000; Qin et al. 2005), independent of their opiate antagonist actions. Other studies find opiate antagonists block TLR4 activation of innate immune transcription, a site of action in innate immune loops (Fig. 2) (Gerald Frank 2011; Hutchinson 2011). Thus, opiate antagonist addiction therapy may be related to inhibition of innate immune responses.
