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.
Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
MeSH terms
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Adenylyl Cyclases / metabolism
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Animals
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Aspartic Acid / metabolism*
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Cocaine / administration & dosage*
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dopamine / metabolism
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Dopamine Uptake Inhibitors / administration & dosage*
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Excitatory Amino Acid Transporter 1 / metabolism
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Excitatory Amino Acid Transporter 2 / metabolism
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Excitatory Amino Acid Transporter 3 / metabolism
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Extracellular Space / drug effects
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Extracellular Space / metabolism
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Gene Expression / drug effects
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Glutamic Acid / metabolism
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Mice
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Phosphorylation / drug effects
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Prefrontal Cortex / drug effects*
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Prefrontal Cortex / metabolism*
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Receptors, Dopamine D1 / metabolism*
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Serine / metabolism
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Signal Transduction / drug effects
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Time Factors
Substances
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Dopamine Uptake Inhibitors
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Drd1 protein, mouse
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2
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Excitatory Amino Acid Transporter 3
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Receptors, Dopamine D1
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Slc1a1 protein, mouse
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Slc1a2 protein, mouse
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Slc1a3 protein, mouse
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Aspartic Acid
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Glutamic Acid
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Serine
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Adenylyl Cyclases
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Cocaine
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Dopamine