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Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine

Nature Neurosciencevolume 4pages12171223 (2001) | Download Citation

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Abstract

A compelling model of experience-dependent plasticity is the long-lasting sensitization to the locomotor stimulatory effects of drugs of abuse. Adaptations in the nucleus accumbens (NAc), a component of the mesolimbic dopamine system, are thought to contribute to this behavioral change. Here we examine excitatory synaptic transmission in NAc slices prepared from animals displaying sensitization 10–14 days after repeated in vivo cocaine exposure. The ratio of AMPA (α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid) receptor- to NMDA (N-methyl-d-aspartate) receptor-mediated excitatory postsynaptic currents (EPSCs) was decreased at synapses made by prefrontal cortical afferents onto medium spiny neurons in the shell of the NAc. The amplitude of miniature EPSCs at these synapses also was decreased, as was the magnitude of long-term depression. These data suggest that chronic in vivo administration of cocaine elicits a long-lasting depression of excitatory synaptic transmission in the NAc, a change that may contribute to behavioral sensitization and addiction.

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Acknowledgements

This work was supported by grants from NIDA (R.M., M.T.) and the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (A.B.). We thank T. Robinson, S. Nicola and G. Hjelmstad for comments on the paper and D. Saal for help with some experiments.

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  1. Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University School of Medicine, Palo Alto, 94304, California, USA

    • Mark J. Thomas
    • , Corinne Beurrier
    •  & Robert C. Malenka
  2. Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, 94110, California, USA

    • Antonello Bonci

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Correspondence to Robert C. Malenka.

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https://doi.org/10.1038/nn757

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