Repeated daily administration of methamphetamine led to development of locomotor sensitization associated with an increased level of PPARγ protein in the nuclear fraction from whole brain tissue, suggesting an increased translocation of the receptor in the nucleus (78). Most notably, repeated intracerebroventricular administration of two distinct PPARγ agonists, pioglitazone and ciglitazone, prevented the expression of methamphetamine sensitization. This protective effect of pioglitazone was synergistically facilitated by concomitant administration of 9-cis-retinoic acid, an agonist for the retinoid X receptor which is another nuclear receptor that forms heterodimers with PPARγ. On the other hand, treatment with the PPARγ antagonist GW9662 during the withdrawal period prior to methamphetamine challenge increased the expression of behavioral sensitization (78).
