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In previous studies, we reported that pretreatment with the antioxidant Tempol attenuated the development and expression of cocaine-induced psychomotor sensitization in rats and diminished cocaine-induced oxidative stress (OS) in the prefrontal cortex (PFC) and nucleus accumbens (NAc), suggesting a potential role for Tempol in interfering with cocaine-related psychomotor sensitization. The aim of the current study was to examine the role of Tempol in reward and reinforcement using the conditioned place preference (CPP) paradigm. We found that administration of Tempol during the conditioning session abolished the expression of cocaine-induced CPP. We also found that OS was significantly elevated following the establishment of CPP, and that cocaine-induced OS was significantly diminished by pretreatment with Tempol during conditioning. Furthermore, we found that repeated, but not single, administration of Tempol for seven days during withdrawal from CPP resulted in significant attenuation in the expression of CPP. Moreover, Tempol did not affect the expression of food reward. Taken together, these findings provide evidence for the involvement of Tempol in regulating cocaine rewarding properties without affecting natural rewards. Since Tempol was found to be effective in reducing OS and expression of CPP following withdrawal, it may be a potential treatment for cocaine addiction.

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