Abstract
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.
Highlights
Cocaine exposure causes structural and functional adaptations within the neural reward circuitry, which seem to be at the core of cocaine use disorder
We show that 10 days of cocaine abstinence with extinction training evoked an increase in the GluN2A subunit levels in the post-synaptic density (PSD) fraction of the prelimbic cortex (PLC) and dorsal hippocampus (dHIP) in rats previously selfadministered cocaine, without any effect on the Grin2A gene expression
It should be noted that the expression of gene Grin2A encoding the GluN2A subunit did not change in rats following the 10-day drug-free period, which suggests that the increased expression of this subunit in the PSD fraction may indicate an increased trafficking of these subunits into the synapse surface rather than increased synthesis of GluN2A
Summary
Cocaine exposure causes structural and functional adaptations within the neural reward circuitry, which seem to be at the core of cocaine use disorder. These neurobiological adaptations in the brain promote craving for cocaine, while dysfunction of reward motivation induces frequent drugtaking. Most research has suggested that the development of substance use disorder is related with cocaine-induced plasticity in the glutamatergic transmission (Bellone and Lüscher 2012; Kalivas 2004). Different neuronal alterations within glutamate signaling (glutamate levels, receptors, and transporters) may be involved in the development of drug craving by enhancing the incentive motivational value of cocaine (Kalivas 2004). Changes in the NMDA receptor subunit composition may represent a potential cellular mechanism leading to cocaine-seeking behavior.
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