4.4 Article

The NMDA Receptor Subunit (GluN1 and GluN2A) Modulation Following Different Conditions of Cocaine Abstinence in Rat Brain Structures

Journal

NEUROTOXICITY RESEARCH
Volume 39, Issue 3, Pages 556-565

Publisher

SPRINGER
DOI: 10.1007/s12640-021-00350-0

Keywords

Cocaine abstinence; Cocaine self-administration; NMDA receptor subunit

Categories

Funding

  1. National Science Centre, Krakow, Poland [UMO2015/17/B/NZ7/02935]

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This study found changes in NMDA receptor subunit levels following cocaine abstinence with extinction training, particularly an increase in GluN2A subunit levels in the postsynaptic density fraction, without changing the expression of Grin1 and Grin2A genes in related brain structures. The modulation of NMDA receptor subunits observed after cocaine abstinence with extinction training may be a potential target for cocaine-seeking behavior.
Different neuronal alterations within glutamatergic system seem to be crucial for developing of cocaine-seeking behavior. Cocaine exposure provokes a modulation of the NMDA receptor subunit expression in rodents, which probably contributes to cocaine-induced behavioral alterations. The aim of this study was to examine the composition of the NMDA receptor subunits in the brain structures in rats with the history of cocaine self-administration after cocaine abstinence (i) in an enriched environment, (ii) in an isolated condition, (iii) with extinction training, or (iv) without instrumental task, as well as the Grin1 (encoding GluN1) and Grin2A (encoding GluN2A) gene expression were evaluated after 10-day extinction training in rat brain structures. In the present study, we observed changes only following cocaine abstinence with extinction training, when the increased GluN2A subunit levels were seen in the postsynaptic density fraction but not in the whole homogenate of the prelimbic cortex (PLC) and dorsal hippocampus (dHIP) in rats previously self-administered cocaine. At the same time, extinction training did not change the Grin1 and Grin2A gene expression in these structures. In conclusion, NMDA receptor subunit modulation observed following cocaine abstinence with extinction training may represent a potential target in cocaine-seeking behavior.

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