Tempol diminishes cocaine-induced oxidative damage and attenuates the development and expression of behavioral sensitization

R. Numa, R. Kohen, T. Poltyrev, R. Yaka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


A variety of mechanisms has been suggested for cocaine toxicity, including the possibility that cocaine induces an increase in oxidative stress (OS) due to excessive oxidation of dopamine (e.g. dopamine quinine), or by redox cycling of cocaine oxidized metabolites. However, the association between oxidative status in the brain and cocaine induced-behavior is poorly understood. Therefore, we examined the ability of the unique antioxidant tempol to attenuate cocaine-induced oxidative damage and behavioral response. Acute cocaine treatment significantly elevated OS markers in prefrontal cortex (PFC) and nucleus accumbens (NAc) in rats, both in slices and following a single cocaine injection, which corresponded with a decrease in total antioxidant capacity (TAC). Tempol, at the optimal concentration we determined that was needed to observe an antioxidant non-toxic effect in vitro (1 mM) and in vivo (200 mg/kg), completely abolished the elevation of OS markers and prevented the reduction in TAC in these areas. Importantly, tempol injections, at a dose that does not affect the basal levels of locomotor activity, attenuated both the development and expression of cocaine-induced locomotor sensitization. Finally, in cocaine-sensitized animals, tempol prevented the elevation of OS markers in both PFC and NAc. Our findings suggest that oxidation of specific sites in the brain reward system by cocaine is accompanied with behavioral changes. Tempol has a neuro-protective effect against cocaine toxicity in these regions, and it may be beneficial in the treatment of cocaine addiction.

Original languageAmerican English
Pages (from-to)649-658
Number of pages10
Issue number3
StatePublished - 26 Aug 2008

Bibliographical note

Funding Information:
This research was partially supported by the Israel Science Foundation (R.Y. grant No. 292/05). R. Kohen and R. Yaka are affiliated with the David R. Bloom Center for Pharmacy and the Brettler Center for research in molecular pharmacology and therapeutics, School of Pharmacy, The Hebrew University of Jerusalem.


  • antioxidants
  • behavioral sensitization
  • cocaine
  • oxidative stress
  • tempol
  • total antioxidant capacity


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