title: Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.
abstract: 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.
authors.affiliation: aDepartment of Pharmacology, Hyogo College of Medicine bDepartment of Pharmacy, Division of Pharmacology, School of Pharmacy, Hyogo University of Health Sciences, Hyogo cMuromachi Kikai Co. Ltd, Tokyo, Japan dMolecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program, Baltimore, Maryland, USA.
authors.forename: Nobue
authors.initials: N
authors.lastname: Kitanaka
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitanaka
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Kaname
authors.initials: K
authors.lastname: Watabe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Motohiko
authors.initials: M
authors.lastname: Takemura
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D051379:Mice; D008813:Mice, Inbred ICR; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors; D014512:Ureohydrolases / Q000037:antagonists & inhibitors
chemical_list: D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D006146:Guanidines; D018377:Neurotransmitter Agents; D010879:Piperazines; C586664:piperazine-1-carboxamidine; D008694:Methamphetamine; D000376:Agmatine; D014512:Ureohydrolases; C019625:agmatinase