Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice

Nobue Kitanaka, Junichi Kitanaka, F. Scott Hall, George R. Uhl, Kaname Watabe, Hitoshi Kubo, Hitoshi Takahashi, Koh Ichi Tanaka, Nobuyoshi Nishiyama, Motohiko Takemura

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


We investigated whether pretreatment with the neurotransmitter/ neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

Original languageEnglish (US)
Pages (from-to)158-165
Number of pages8
JournalBehavioural Pharmacology
Issue number2
StatePublished - 2014
Externally publishedYes


  • agmatinase inhibitor
  • agmatine
  • hyperlocomotion methamphetamine
  • mouse
  • stereotyped behavior

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Medicine(all)


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