Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.

Abstract

Dopamine and glutamate play critical roles in the reinforcing effects of cocaine. We demonstrated that a single intraperitoneal administration of cocaine induces a significant decrease in [(3)H]-d-aspartate uptake in the pre-frontal cortex (PFC). This decrease is associated with elevated dopamine levels, and requires dopamine D1-receptor signaling (D1R) and adenylyl cyclase activation. The effect was observed within 10min of cocaine administration and lasted for up to 30min. This rapid response is related to D1R-mediated cAMP-mediated activation of PKA and phosphorylation of the excitatory amino acid transporters EAAT1, EAAT2 and EAAT3. We also demonstrated that cocaine exposure increases extracellular d-aspartate, l-glutamate and d-serine in the PFC. Our data suggest that cocaine activates dopamine D1 receptor signaling and PKA pathway to regulate EAATs function and extracellular EAA level in the PFC.

DOI: 10.1016/j.neuroscience.2016.05.022

Cite this paper

@article{Sathler2016SingleET, title={Single exposure to cocaine impairs aspartate uptake in the pre-frontal cortex via dopamine D1-receptor dependent mechanisms.}, author={Matheus F Sathler and Bernardo Stutz and Robertta Silva Martins and Maur{\'i}cio dos Santos Pereira and Ney Roner Pecinalli and Lu{\'i}s Eduardo Santos and Rosilane Taveira-da-Silva and Jennifer Lowe and Isis Grigorio de Freitas and Ricardo Augusto De Melo Reis and Alex Christian Manh{\~a}es and Regina C{\'e}lia Cussa Kubrusly}, journal={Neuroscience}, year={2016}, volume={329}, pages={326-36} }