There are three closely related isoforms of PPARs: PPARα, PPARδ (β) and PPARγ. Each is encoded by a different gene and has a unique tissue distribution, but all have been identified in the CNS (Schnegg and Robbins, 2011), and PPAR activity in the brain is relatively high (Kao et al., 2012). PPAR agonists have been highlighted in the treatment of several CNS diseases, including Alzheimer's, Parkinson's and Huntington's disease, schizophrenia, and ischemic brain injury (Mandrekar-Colucci et al., 2013). The PPARα agonist gemfibrozil decreased voluntary alcohol consumption in rats (Barson et al., 2009), and PPARγ agonists (pioglitazone and rosiglitazone) reduced voluntary alcohol consumption (Stopponi et al., 2011; Stopponi et al., 2013) and decreased stress-induced relapse and alcohol withdrawal symptoms in alcohol-dependent rats (Stopponi et al., 2011). PPAR agonists are also promising medications for the treatment of different drug addictions in many preclinical studies (Le Foll et al., 2013). Furthermore, expression of PPARδ and PGC-1α, the coactivator of PPARγ, is altered in brains of human alcoholics (Ponomarev et al., 2012), and PGC-1α is also altered in other neurodegenerative diseases (Austin and St-Pierre, 2012).
