Prenatal Cocaine Reduces AMPA Receptor Synaptic Expression ...

Abstract

Prenatal cocaine exposure produces sustained neurobehavioral and brain synaptic changes closely resembling those of animals with defective AMPA receptors (AMPARs). We hypothesized that prenatal cocaine exposure attenuates AMPAR signaling by interfering with AMPAR synaptic targeting. AMPAR function is governed by receptor cycling on and off the synaptic membrane through its interaction with glutamate receptor-interacting protein (GRIP), a PDZ domain protein that is regulated by reversible phosphorylation. Our results show that prenatal cocaine exposure markedly reduces AMPAR synaptic targeting and attenuates AMPAR-mediated synaptic long-term depression in the frontal cortex of 21-d-old rats. This cocaine effect is the result of reduced GRIP–AMPAR interaction caused by persistent phosphorylation of GRIP by protein kinase C (PKC) and Src tyrosine kinase. These data support the restoration of AMPAR activation via suppressing excessive PKC-mediated GRIP phosphorylation as a novel therapeutic approach to treat the neurobehavioral consequences of prenatal cocaine.


Osteopathic School Of Medicine Stratford Nj - Bookshelf

Of mice and men

Of mice and men

The tragic story of the friendship between two migrant workers, George and mentally retarded Lenny, and their dream of owning a farm

Three Cups of Tea

Three Cups of Tea


Elements of Style

Elements of Style

The Elements of Style is a classic work which is intended for use in English courses in which the practice of composition is combined with the study of ...

The Grapes of Wrath

The Grapes of Wrath

Depicts the hardships and suffering endured by the Joads as they journey from Oklahoma to California during the Depression.

A Confederacy of Dunces

A Confederacy of Dunces

The novel astonishes with its inventiveness; it lives in the play of its voices. A Confederacy of Dunces is nothing less than a grand comic fugue.

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School of Osteopathic Medicine at UMDNJ
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