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 (alpha-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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Behavior, Animal / physiology
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Cocaine / pharmacology*
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Cocaine-Related Disorders / metabolism*
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Cocaine-Related Disorders / physiopathology
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Dose-Response Relationship, Drug
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Drug Tolerance / physiology*
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Male
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Mice
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Mice, Inbred C57BL
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Motor Activity / drug effects
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Motor Activity / physiology
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Neural Inhibition / drug effects*
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Neural Inhibition / physiology
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Neural Pathways / drug effects
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Neural Pathways / metabolism
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Neuronal Plasticity / drug effects*
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Neuronal Plasticity / physiology
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / metabolism
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Nucleus Accumbens / physiopathology
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism
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Presynaptic Terminals / drug effects*
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Presynaptic Terminals / metabolism
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Cocaine