Pretreatment with LY2090314, a potent glycogen synthase kinase-3 inhibitor, suppresses methamphetamine-induced stereotyped behavior but not hyperlocomotion in mice.

IF 1.6 4区心理学 Q3 BEHAVIORAL SCIENCES

Behavioural Pharmacology Pub Date : 2025-09-25 DOI:10.1097/FBP.0000000000000853

Kentaro Matsuda, Nobue Kitanaka, Frank Scott Hall, Takahiro Hamana, Masanori Nakai, Sho Yuze, Kazuo Tomita, Kento Igarashi, Tomoaki Sato, George R Uhl, Junichi Kitanaka

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引用次数: 0

Abstract

Neuronal glycogen synthase kinase-3s (GSK-3α and the more abundant GSK-3β) are serine/threonine kinases that have been postulated to play roles in neuronal adaptations, including those that come from exposures to substances of abuse; however, there is only modest information about ways in which GSK-3 alters the effects of the widely abused psychostimulant, methamphetamine (METH). To evaluate the effects of GSK-3 inhibition on METH-induced symptoms, mice were treated with LY2090314, a potent and selective GSK-3 inhibitor, followed by METH. Horizontal locomotion, vertical rearing, and stereotyped behaviors were measured. Pretreatment with LY2090314 (2.5, 10, and 25 mg/kg) significantly inhibited stereotypic behavior induced by METH (10 mg/kg) in a dose-dependent fashion. Stereotyped biting was most robustly reduced by LY2090314. By contrast, LY2090314 had no significant effect on METH (3 mg/kg)-induced hyperlocomotion. GSK-3 signaling pathways appear to be differentially involved in acute METH effects on locomotion. GSK-3 appears essential for the expression of METH-induced stereotypy but not hyperlocomotion.

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LY2090314（一种有效的糖原合成酶激酶3抑制剂）预处理可以抑制甲基苯丙胺诱导的小鼠刻板行为，但不能抑制过度运动。

神经元糖原合成酶激酶-3 （GSK-3α和更丰富的GSK-3β）是丝氨酸/苏氨酸激酶，被认为在神经元适应中发挥作用，包括那些来自滥用物质暴露的神经元；然而，关于GSK-3如何改变被广泛滥用的精神兴奋剂甲基苯丙胺（methamphetamine，简称冰毒）的作用，目前只有有限的信息。为了评估GSK-3抑制对甲基苯丙胺诱导的症状的影响，我们用一种强效和选择性的GSK-3抑制剂LY2090314治疗小鼠，然后用甲基苯丙胺治疗。测量水平运动、垂直饲养和刻板印象行为。LY2090314预处理（2.5、10和25 mg/kg）显著抑制甲基安非他明（10 mg/kg）诱导的刻板行为，且呈剂量依赖性。LY2090314对刻板咬伤的抑制作用最为显著。相比之下，LY2090314对冰毒（3 mg/kg）诱导的过度运动无显著影响。GSK-3信号通路似乎不同地参与了急性甲基苯丙胺对运动的影响。GSK-3似乎对甲基甲醚诱导的刻板印象的表达至关重要，而不是过度运动的表达。

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来源期刊

Behavioural Pharmacology 医学-行为科学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.