Behavioral phenotyping and dopamine dynamics in mice with conditional deletion of the glutamate transporter GLT-1 in neurons: resistance to the acute locomotor effects of amphetamine

Psychopharmacology
Kathryn D FischerPaul A Rosenberg

Abstract

GLT-1 is the major glutamate transporter in the brain and is expressed predominantly in astrocytes but is also present in excitatory axon terminals. To understand the functional significance of GLT-1 expressed in neurons, we generated a conditional GLT-1 knockout mouse and inactivated GLT-1 in neurons using Cre-recombinase expressed under the synapsin 1 promoter, (synGLT-1 KO). Abnormalities of glutamate homeostasis have been shown to affect hippocampal-related behaviors including learning and memory as well as responses to drugs of abuse. Here, we asked whether deletion of GLT-1 specifically from neurons would affect behaviors that assessed locomotor activity, cognitive function, sensorimotor gating, social interaction, as well as amphetamine-stimulated locomotor activity. We found that the neuronal GLT-1 KO mice performed similarly to littermate controls in the behavioral tests we studied. Although performance in open field testing was normal, the acute locomotor response to amphetamine was significantly blunted in the synGLT-1 KO (40% of control). We found no change in amphetamine-stimulated extracellular dopamine in the medial shell of the nucleus accumbens, no change in electrically stimulated or amphetamine-induced dopami...Continue Reading

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Citations

Oct 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Abhijeet SharmaAna C Pereira
Mar 31, 2019·Nature Communications·J A GomezC A Paladini
Nov 8, 2020·Neurochemistry International·Kathryn D FischerPaul A Rosenberg
Apr 28, 2021·Neurochemical Research·Niels Christian DanboltYun Zhou
May 1, 2021·Frontiers in Cellular Neuroscience·Renae M RyanAnnalisa Scimemi
Sep 3, 2021·Nature Communications·Kevin UngBenjamin R Arenkiel

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Methods Mentioned

BETA
transgenic
Protein Assay

Software Mentioned

Digigate
IGOR Pro
WaveMetrics
GraphPad Prism
Maze
Ethovision XT
DigiGait
Any

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