In order to further investigate the role of the mPFC in morphine reward and drug priming induced relapse, the present study examined the effects of the mPFC lesions on the acquisition and morphine priming induced reinstatement of conditioned place preference (CPP). In the first experiment, mice received sham or bilateral kainic acid lesions of the mPFC and were subsequently tested for the acquisition of a morphine-induced CPP. In the second experiment, each mouse received lesions of mPFC following the establishment of morphine-induced CPP. Nine days later, a priming injection of morphine was given (2 mg/kg, i.p.) to reinstate the extinguished CPP. The results showed that pre-conditioning lesions of the mPFC blocked the acquisition of morphine-induced CPP, while post-conditioning lesions of the mPFC failed to prevent morphine priming induced reinstatement of CPP. These results provide the first direct evidence that the mPFC may be involved in the acquisition, but not morphine priming induced reinstatement of CPP. (c) 2007 Elsevier Ireland Ltd. All rights reserved.