Blockade by naloxone of cocaine-induced hyperactivity, reverse tolerance and conditioned place preference in mice

Hack Seang Kim, Woo Kyu Park, Choon Gon Jang, Ki Wan Oh, Jae Yang Kong, Seikwan Oh, Hang Mook Rheu, Dae Hyun Cho, Seog Youn Kang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Cocaine-induced hyperactivity was inhibited by a single administration of naloxone (2 and 5 mg/kg, i.p.), an opioid receptor antagonist, and naloxone administered prior to and during the chronic injection of cocaine attenuated the development of both cocaine-induced reverse tolerance and conditioned place preference (CPP). Dopamine (DA) receptor supersensitivity which developed in cocaine-induced reverse tolerant or CPP mice, was also inhibited by naloxone. Furthermore, naloxone reduced an apomorphine-induced striatal dopaminergic action, climbing behavior. Therefore, the present studies suggest that cocaine-induced dopaminergic behaviors, such as hyperactivity, reverse tolerance and CPP, may be commonly produced via activation of an opioid receptor. The development of DA receptor supersensitivity may be a possible common mechanism of cocaine-induced reverse tolerance and CPP, since cocaine-induced changes in sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in mice, were both inhibited by naloxone.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalBehavioural Brain Research
Issue number1
StatePublished - Apr 1997

Bibliographical note

Funding Information:
This researchw as supportedin part by a grant (1996-1997f)r om the ResearchC enterf or New Drug DevelopmentC,o llege of PharmacyS, eoul National UniversityR, epublico f Korea.


  • apomorphine
  • climbing behavior
  • cocaine
  • conditioned place preference
  • dopamine receptor supersensitivity
  • hyperactivity
  • naloxone
  • reverse tolerance


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