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Prenatal cocaine reduces AMPA receptor synaptic expression through hyperphosphorylation of the synaptic anchoring

Kalindi Bakshi1, Serena Gennaro, Christopher Y Chan

  • 1Department of Physiology, The City University of New York Medical School, New York, New York 10031, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|May 15, 2009
PubMed

Insights

Prenatal cocaine exposure impairs brain function by disrupting AMPA receptor (AMPAR) signaling. This study reveals that cocaine exposure reduces AMPAR synaptic targeting, offering a potential therapeutic target for neurobehavioral issues.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Biology

Background:

  • Prenatal cocaine exposure causes lasting neurobehavioral and synaptic changes.
  • These changes mimic those seen in animals with deficient AMPA receptors (AMPARs).

Purpose of the Study:

  • To investigate if prenatal cocaine exposure disrupts AMPAR signaling by affecting synaptic targeting.
  • To identify the molecular mechanisms underlying cocaine-induced AMPAR dysfunction.

Main Methods:

  • Examined AMPAR synaptic targeting and function in the frontal cortex of rats exposed to cocaine prenatally.
  • Investigated the interaction between AMPAR and GRIP (glutamate receptor-interacting protein).
  • Assessed the phosphorylation status of GRIP by protein kinase C (PKC) and Src tyrosine kinase.

Main Results:

  • Prenatal cocaine exposure significantly reduced AMPAR synaptic targeting and AMPAR-mediated synaptic long-term depression in the frontal cortex.
  • Cocaine exposure led to decreased GRIP-AMPAR interaction due to persistent GRIP phosphorylation by PKC and Src.
  • These molecular changes underlie the observed synaptic and functional deficits.

Conclusions:

  • Prenatal cocaine exposure disrupts AMPAR synaptic function through altered GRIP phosphorylation.
  • Restoring AMPAR activation by inhibiting excessive GRIP phosphorylation presents a potential therapeutic strategy for prenatal cocaine exposure consequences.

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