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

Neuroscience. 2016 Aug 4;329:326-36. doi: 10.1016/j.neuroscience.2016.05.022. Epub 2016 May 18.

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.

Keywords: cocaine; dopamine; glutamate; prefrontal cortex; transporter.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Aspartic Acid / metabolism*
  • Cocaine / administration & dosage*
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Excitatory Amino Acid Transporter 3 / metabolism
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Gene Expression / drug effects
  • Glutamic Acid / metabolism
  • Mice
  • Phosphorylation / drug effects
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism*
  • Receptors, Dopamine D1 / metabolism*
  • Serine / metabolism
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Dopamine Uptake Inhibitors
  • Drd1 protein, mouse
  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • Excitatory Amino Acid Transporter 3
  • Receptors, Dopamine D1
  • Slc1a1 protein, mouse
  • Slc1a2 protein, mouse
  • Slc1a3 protein, mouse
  • Aspartic Acid
  • Glutamic Acid
  • Serine
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Cocaine
  • Dopamine