Kitanaka Nobue, Kitanaka Junichi, Hall F Scott, Uhl George R, Watabe Kaname, Kubo Hitoshi, Takahashi Hitoshi, Tanaka Koh-ichi, Nishiyama Nobuyoshi, Takemura Motohiko
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.
Behav Pharmacol. 2014 Apr;25(2):158-65. doi: 10.1097/FBP.0000000000000030.
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.
我们研究了用神经递质/神经调质胍丁胺（脱羧L-精氨酸）进行预处理是否会影响雄性ICR小鼠中甲基苯丙胺（METH）诱导的运动亢进和刻板行为。单独使用胍丁胺预处理对运动或刻板行为没有影响，但它能剂量依赖性地减弱低剂量METH（5毫克/千克）诱导的运动和刻板行为的总发生率。该剂量诱导的刻板行为主要表现为刻板嗅闻。相比之下，胍丁胺不影响高剂量METH（10毫克/千克）诱导的刻板行为的总发生率。然而，该剂量METH诱导的刻板行为的性质发生了显著改变；胍丁胺预处理显著减少了刻板咬噬，但显著增加了刻板嗅闻和持续运动。因此，胍丁胺预处理似乎使METH的剂量-反应曲线向右移动。用哌嗪-1-甲脒（一种假定的胍丁胺酶抑制剂）预处理小鼠对低剂量METH诱导的运动或刻板行为没有影响，这表明内源性胍丁胺可能不调节METH的作用。
