The selective μ opioid receptor antagonist β-funaltrexamine attenuates methamphetamine-induced stereotypical biting in mice

Junichi Kitanaka, Nobue Kitanaka, F. Scott Hall, George R. Uhl, Yuko Fukushima, Tatsuo Sawai, Kaname Watabe, Hitoshi Kubo, Hitoshi Takahashi, Koh Ichi Tanaka, Nobuyoshi Nishiyama, Tomohiro Tatsuta, Yoshio Morita, Motohiko Takemura

Research output: Contribution to journalArticlepeer-review


We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration. Thus, METH-induced stereotypical sniffing and persistent locomotion were significantly increased by naloxone treatment while stereotypical biting was reduced. One way to interpret this pattern of effects is that pretreatment with naloxone appeared to produce a shift in the dose-response curve for METH. Thus, while the more intense forms of oral-facial stereotypies were reduced, increased persistent locomotion was observed in mice given naloxone followed by METH. The selective μ opioid receptor antagonist β-funaltrexamine, but not nor-binaltorphimine (a κ-selective antagonist) nor naltrindole (a δ-selective antagonist), mimicked the effect of naloxone. These observations suggest that opioid receptor antagonists may attenuate METH-induced stereotypical biting in mice via μ opioid receptors, and suggest that antagonism of this system may be a potential therapeutic approach to reducing some deleterious effects of METH use and perhaps in the treatment of some forms of self-injurious behavior.

Original languageEnglish (US)
Pages (from-to)88-98
Number of pages11
JournalBrain Research
StatePublished - Jul 19 2013
Externally publishedYes


  • μ Opioid receptor
  • Endogenous opioid system
  • Methamphetamine
  • Stereotypical behavior

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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