GLT-1阳性变构调节剂降低小鼠甲基苯丙胺过度运动、致敏和条件性位置偏好。

IF 2.4 4区医学 Q3 NEUROSCIENCES

Neuroscience Research Pub Date : 2025-01-31 DOI:10.1016/j.neures.2025.01.008

Prateek Mokkarala , Sonita Wiah , Ellen M. Unterwald , Xiangdang Shi , Danielle R. Stern , Andreia C.K. Fontana , Joseph M. Salvino , Scott M. Rawls

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引用次数: 0

摘要

NA-014是谷氨酸转运蛋白亚型1 （GLT-1）的正变构调节剂（PAM），可增加谷氨酸再摄取。由于谷氨酸的增强传递促进了甲基苯丙胺（METH）的过度运动、行为致敏和条件性位置偏好（CPP），我们假设NA-014 （60mg/kg）可以减轻雄性小鼠的这些影响。NA-014减少甲基苯丙胺引起的急性活动和重复甲基苯丙胺的行为致敏。甲基化后给药的NA-014降低了甲基化CPP的表达。甲基安非他明条件下注射NA-014不影响甲基安非他明CPP的发育，NA-014不影响空间记忆。这些结果表明，GLT-1 PAMs可以减少甲胺素引起的小鼠行为影响。

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Positive allosteric modulator of GLT-1 reduces methamphetamine hyperlocomotion, sensitization and conditioned place preference in mice

NA-014 is a positive allosteric modulator (PAM) of glutamate transporter subtype 1 (GLT-1) that increases glutamate reuptake. Since enhanced glutamate transmission facilitates methamphetamine (METH) hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP), we hypothesized that NA-014 (60 mg/kg) would reduce these effects in male mice. NA-014 reduced acute ambulation induced by METH and behavioral sensitization during repeated METH. NA-014 given after METH conditioning reduced expression of METH CPP. NA-014 injected during METH conditioning did not affect development of METH CPP, and NA-014 did not affect spatial memory. These results suggest that GLT-1 PAMs reduce METH-induced behavioral effects in mice.

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来源期刊

Neuroscience Research 医学-神经科学

CiteScore

5.60

自引率

3.40%

发文量

136

审稿时长

28 days

期刊介绍： The international journal publishing original full-length research articles, short communications, technical notes, and reviews on all aspects of neuroscience Neuroscience Research is an international journal for high quality articles in all branches of neuroscience, from the molecular to the behavioral levels. The journal is published in collaboration with the Japan Neuroscience Society and is open to all contributors in the world.