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Positive allosteric modulator of GLT-1 reduces methamphetamine hyperlocomotion, sensitization and conditioned place preference in mice
Journal article   Open access   Peer reviewed

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

Prateek Mokkarala, Sonita Wiah, Ellen M Unterwald, Xiangdang Shi, Danielle Stern, Andreia C.K. Fontana, Joseph M. Salvino and Scott M. Rawls
Neuroscience research, v 213, pp 156-160
Apr 2025
PMID: 39894415
url
https://doi.org/10.1016/j.neures.2025.01.008View
Published, Version of Record (VoR) Open

Abstract

CPP GLT-1 glutamate locomotor methamphetamine NA-014 PAM
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 (60mg/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. •Positive allosteric modulator (PAM) of GLT-1was investigated in mice.•NA-014 (PAM GLT-1) reduced methamphetamine ambulation.•NA-014 reduced methamphetamine behavioral sensitization.•NA-014 reduced expression of methamphetamine CPP.•NA-014 is first GLT-1 PAM to display efficacy against methamphetamine.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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