Contrasting the Role of xCT and GLT-1 Upregulation in the Ability of Ceftriaxone to Attenuate the Cue-Induced Reinstatement of Cocaine Seeking and Normalize AMPA Receptor Subunit Expression

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Amber L LaCrosseLori Knackstedt

Abstract

Long-term treatment with ceftriaxone attenuates the reinstatement of cocaine seeking while increasing the function of the glutamate transporter 1 (GLT-1) and system xC- (Sxc) in the nucleus accumbens core (NAc). Sxc contributes the majority of nonsynaptic extracellular glutamate in the NAc, while GLT-1 is responsible for the majority of glutamate uptake. Here we used antisense to decrease the expression of GLT-1 and xCT (a catalytic subunit of Sxc) to determine the relative importance of both proteins in mediating the ability of ceftriaxone to prevent cue-induced reinstatement of cocaine seeking and normalize glutamatergic proteins in the NAc of rats. Intra-NAc xCT knockdown prevented ceftriaxone from attenuating reinstatement and from upregulating GLT-1 and resulted in increased surface expression of AMPA receptor subunits GluA1 and GluA2. Intra-NAc GLT-1 knockdown also prevented ceftriaxone from attenuating reinstatement and from upregulating xCT expression, without affecting GluA1 and GluA2 expression. In the absence of cocaine or ceftriaxone treatment, xCT knockdown in the NAc increased the expression of both GluA1 and GluA2 without affecting GLT-1 expression while GLT-1 knockdown had no effect. PCR and immunoprecipitation ...Continue Reading

Citations

Jul 3, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Bethany A StennettLori A Knackstedt
Sep 25, 2017·NPJ Schizophrenia·Sinead M O'DonovanRobert E McCullumsmith
Jul 25, 2019·Frontiers in Molecular Neuroscience·Allison R Peterson, Devin K Binder
Dec 29, 2020·Pharmacology & Therapeutics·Ewa Niedzielska-AndresEdmund Przegaliński
Nov 8, 2020·Neurochemistry International·Kathryn D FischerPaul A Rosenberg
Feb 19, 2021·Pharmacological Reviews·Mariana Angoa-Pérez, Donald M Kuhn
Feb 21, 2019·Drug and Alcohol Dependence·Allison R Bechard, Lori A Knackstedt
Apr 9, 2021·Frontiers in Neurology·Oscar B AlcorezaHarald Sontheimer
Oct 11, 2017·Progress in Neuro-psychopharmacology & Biological Psychiatry·Ronald KimKathryn J Reissner
Aug 31, 2020·Current Opinion in Pharmacology·Anna Kruyer, Peter W Kalivas
Jul 3, 2021·International Journal of Molecular Sciences·Marek Schwendt, Lori A Knackstedt
May 15, 2021·The Journal of Pharmacology and Experimental Therapeutics·Lori A KnackstedtMagid Abou-Gharbia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.