Nature Neuroscience4, 1217 - 1223 (2001)
Published online: 5 November 2001; | doi:10.1038/nn757
Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine
Mark J. Thomas1, Corinne Beurrier1, Antonello Bonci2
& Robert C. Malenka1
1
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304, USA
2
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, California 94110, USA
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 (-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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