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

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12640-021-00350-0.