Blockade of Glutamate Receptors within the Prelimbic Cortex Attenuate Concentration of Excitatory Amino Acids in the Morphine Self-administration in Rats

Abstract

Background:The attitude of research on addiction has been done on the key role of glutamate. As a regard, the prelimbic cortex (PrL) has an important role in addiction, learning, and memory. We tried to investigate the level of glutamate and aspartate concentration after glutamate receptors blockade in this region in the morphine-addicted rats.Materials and Methods:In this study, we examined the effects of local infusion of the N-methyl-D-aspartate receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, 2-amino-5-phosphonovaleric acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), into the PrL cortex on the level of excitatory amino acids (EAAs) and glycine. After 11 days of self-administration, the prelimbic area of the brain was taken out, and the EAAs and glycine concentration was measured by high-performance liquid chromatography.Results:Morphine resulted in the significant increase in the EAAs concentration within this area (P ≤ 0.001). Microinjection of AP5 into this region before using of morphine significantly decreased the morphine-induced glutamate and aspartate concentration (P ≤ 0.001). CNQX had the same effect and significantly reduced the EAAs concentration compared to the morphine group (P ≤ 0.001). In addition, microinjection of AP5 and CNQX simultaneously increased glycine concentration (P ≤ 0.001).Conclusions:These results show that morphine stimulates the EAAs release in the prelimbic area. It seems that microinjection of AP5 or CNQX in this region is effective in reducing morphine-induced EAA. It is suggested that EAA transmission in the PrL cortex may be a possible target for treatment of morphine addiction.

Protracted morphine withdrawal corresponds with sex-specific alterations to motivated behavior and mesoaccumbal subcircuit dopamine cell plasticity

“…Additionally, neuroadaptations to VTA DA cells have been previously shown to alter behavior towards both natural and opioid reward following endogenous opioidergic signaling, suggesting supranatural levels of opioids such as those used here have the potential to meet if not exceed such effects 62 . Related alterations in motivated behavior, whereby preference for and consumption of opioids surpasses that of non-drug rewards (e.g., food, exercise), is thought to be a predominant factor conferring vulnerability to escalated drug use and relapse 28,[63][64][65][66][67][68][69][70][71][72][73][74][75][76] .…”