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Objective The medial prefrontal cortex (mPFC) and dorsal hippocampus (DHC) play significant roles in stimulant-induced neurobehavioral effects.In order to investigate the role of mPFC and DHC in methamphetamine (MAP) reward and drug-priming induced relapse, the present study examined the effect of lesions of mPFC or DHC on the acquisition and MAP priming induced reinstatement of conditioned place preference (CPP) in mice.Methods After pre-training or establishment day of CPP, the animals received bilateral kainic acid (KA) or N-methyl-d-aspartate (NMDA) lesions of mPFC or DHC.Results The results showed that both KA and NMDA lesions of mPFC significantly blocked the acquisition of MAP-induced CPP, and a KA but not NMDA lesion of the DHC prevented the acquisition of MAP-induced CPP.Moreover, the MAP priming induced CPP-reinstatement was prevented by a KA but not NMDA lesion of mPFC, and was markedly inhibited by only an NMDA lesion of DHC.Conclusion These findings indicated that the ionotropic glutamate receptors (iGluRs) in mPFC and DHC were involved in MAP-induced CPP.Moreover, different types of iGluRs in these two regions may be participated in acquisition and MAP-priming induced reinstatement of CPP, respectively.