Several FDA-approved drugs with anti-inflammatory and immune inhibitory actions (Fig. 1) have been shown to modulate alcohol responses in animal models. For example, the antibiotics minocycline and doxycycline are anti-inflammatory and modestly decrease alcohol consumption in mice, increase sensitivity to the motor-impairing effects of alcohol, and decrease alcohol-induced sedation [50–52]. Anakinra, the IL-1 receptor antagonist used in the treatment of rheumatoid arthritis, also reduces alcohol-induced sedation in mice [52]. The anticonvulsant topiramate is anti-inflammatory and decreases alcohol consumption in alcohol-preferring rats [53–55] and improves treatment outcome in alcoholics [56,57]. Moreover, indomethacin, a cyclooxygenase enzyme inhibitor and non-steroidal anti-inflammatory, reduces induction of innate immune genes and decreases behavioral deficits in rats exposed to ethanol [58]. Pioglitazone treats insulin resistance and diabetes and is an agonist of peroxisome proliferator-activated type gamma receptors (PPAR) located on neurons and glia in brain. PPAR activation reduces innate immune signaling, and pioglitazone suppresses alcohol drinking and relapse to alcohol seeking in rats [59]. Additional subtypes of PPAR agonists may prove effective in the treatment of addictions given that clofibrate, a PPAR alpha agonist, blocks the rewarding
