Locomotor sensitization to cocaine is associated with distinct pattern of glutamate receptor trafficking to the postsynaptic density in prefrontal cortex: Early versus late withdrawal effects |
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Authors: | M Behnam Ghasemzadeh Preethi Vasudevan Christopher Mueller |
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Institution: | Department of Biomedical Sciences, Integrative Neuroscience Research Center, Marquette University, Milwaukee, WI 53201, United States |
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Abstract: | Glutamatergic neurotransmission plays an important role in the behavioral and molecular plasticity observed in cocaine mediated locomotor sensitization. Recent studies show that glutamatergic signaling is regulated by receptor trafficking, synaptic localization, and association with scaffolding proteins. The trafficking of the glutamate receptors was investigated in the dorsal and ventral prefrontal cortex at 1 and 21 days after repeated cocaine administration which produced robust locomotor sensitization. A subcellular fractionation technique was used to isolate the cellular synaptosomal fraction containing the postsynaptic density. At early withdrawal, the prefrontal cortex displayed a reduction in the synaptosomal content of the AMPA and NMDA receptor subunits. In contrast, after extended withdrawal, there was a significant increase in the trafficking of the receptors into the synaptosomal compartment. These changes were accompanied by corresponding trafficking of the postsynaptic glutamatergic scaffolding proteins. Thus, enhanced trafficking of glutamate receptors from cytosolic to synaptosomal compartment is associated with prolonged withdrawal from repeated exposure to cocaine and may have functional consequences for the synaptic and behavioral plasticity. |
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Keywords: | AMPA NMDA mGluR5 Addiction Scaffolding proteins Synaptic plasticity Prefrontal cortex Anterior cingulate cortex Cocaine Locomotor sensitization Postsynaptic density |
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