Two studies have looked at the role of PPAR-α receptors in sensitization. In one study, mutant mice lacking the PPAR-α gene were tested for sensitization to injections of morphine and cocaine. It was found that, in these mutant mice, sensitization to cocaine was unaffected (71). However, in mutant mice lacking the PPAR-α gene, sensitization to morphine was potentiated (71). Increased sensitization to morphine was observed at a dose of 5 mg/kg but, at a higher dose of 10 mg/kg, sensitization in the mutant was not different from that in the wild-type. Therefore, deletion of PPAR-α gene may enhance sensitization. Further, these effects may be evident only after the acquisition of sensitization, because when the PPAR-α agonist WY14643 was administered prior to either induction or expression of sensitization, it blocked the expression but not the acquisition of sensitization to morphine.
