Evidence map›Paper›PMID 37251646›Full record

ArticleFrontiers in molecular neuroscience2023

Glutamate dynamics in the dorsolateral striatum of rats with goal-directed and habitual cocaine-seeking behavior.

Danielle M Giangrasso, Kaliana M Veros, Maureen M Timm, Peter J West, Karen S Wilcox, Kristen A Keefe

Open access · goldAbstract read
In one paragraph

Article in Frontiers in molecular neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 90% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 0 citations in OpenAlex.

  1. Article
4 · The record

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5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Danielle M GiangrassoDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
Kaliana M VerosDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
Maureen M TimmDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
Peter J WestDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
Karen S WilcoxDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
Kristen A KeefeDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, UT, United States.
University of Utah · US

Funding

The Neuroimmunology Training Program at the University of UtahT32NS115664 · NINDS · UNIVERSITY OF UTAH · PI O'CONNELL, RYAN M, WILCOX, KAREN S · 2020 to 2024
$988k
NINDS NIH HHS T32 NS115664
6 · The paper itself

Abstract

The shift from drug abuse to addiction is considered to arise from the transition between goal-directed and habitual control over drug behavior. Habitual responding for appetitive and skill-based behaviors is mediated by potentiated glutamate signaling in the dorsolateral striatum (DLS), but the state of the DLS glutamate system in the context of habitual drug-behavior remains undefined. Evidence from the nucleus accumbens of cocaine-experienced rats suggests that decreased transporter-mediated glutamate clearance and enhanced synaptic glutamate release contribute to the potentiated glutamate signaling that underlies the enduring vulnerability to relapse. Preliminary evidence from the dorsal striatum of cocaine-experienced rats suggests that this region exhibits similar alterations to glutamate clearance and release, but it is not known whether these glutamate dynamics are associated with goal-directed or habitual control over cocaine-seeking behavior. Therefore, we trained rats to self-administer cocaine in a chained cocaine-seeking and -taking paradigm, which yielded goal-directed, intermediate, and habitual cocaine-seeking rats. We then assessed glutamate clearance and release dynamics in the DLS of these rats using two different methods: synaptic transporter current (STC) recordings of patch-clamped astrocytes and the intensity-based glutamate sensing fluorescent reporter (iGluSnFr). While we observed a decreased rate of glutamate clearance in STCs evoked with single-pulse stimulation in cocaine-experienced rats, we did not observe any cocaine-induced differences in glutamate clearance rates from STCs evoked with high frequency stimulation (HFS) or iGluSnFr responses evoked with either double-pulse stimulation or HFS. Furthermore, GLT-1 protein expression in the DLS was unchanged in cocaine-experienced rats, regardless of their mode of control over cocaine-seeking behavior. Lastly, there were no differences in metrics of glutamate release between cocaine-experienced rats and yoked-saline controls in either assay. Together, these results suggest that glutamate clearance and release dynamics in the DLS are largely unaltered by a history of cocaine self-administration on this established cocaine seeking-taking paradigm, regardless of whether the control over the cocaine seeking behavior was habitual or goal directed.

Indexed as

astrocytescocainedevaluationdorsal striatumglutamate transporterhabitual and goal-directed processesiGluSnFrsynaptic transport currents

Identifiers

PMID37251646
PMCPMC10213946
OpenAlexW4376278990

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.