Regulation of AMPA receptor trafficking in the nucleus accumbens by dopamine and cocaine

Research output: Contribution to journalReview article

44 Citations (Scopus)

Abstract

Nucleus accumbens (NAc) neurons are excited primarily by AMPA-type glutamate receptors (AMPAR). This is required for cocaine seeking in animal models of cocaine addiction, suggesting AMPAR transmission in the NAc as a key control point for cocaine-related behaviors. This review will briefly describe AMPAR properties and trafficking, with a focus on studies in NAc neurons, and then consider mechanisms by which cocaine may alter AMPAR transmission. Two examples will be discussed that may be important in two different stages of addiction: learning about drugs and drug-related cues during the period of drug exposure, and persistent vulnerability to craving and relapse after abstinence is achieved. The first example is drawn from studies of cultured NAc neurons. Elevation of dopamine levels (as would occur following cocaine exposure) facilitates activity-dependent strengthening of excitatory synapses onto medium spiny neurons, the main cell type and projection neuron of the NAc. This occurs because activation of D1-class dopamine receptors primes AMPAR for synaptic insertion. This may create a temporal window in which stimuli related to cocaine-taking are more efficacious at eliciting synaptic plasticity and thus being encoded into memory. The second example involves rat models of cocaine addiction. Cell surface and synaptic expression of AMPAR on NAc neurons is persistently increased after withdrawal from repeated cocaine exposure. We hypothesize that this increases the reactivity of NAc neurons to glutamate inputs from cortex and limbic structures, facilitating the ability of these inputs to trigger cocaine seeking and thus contributing to the persistent vulnerability to relapse that characterizes addiction.

Original languageEnglish (US)
Pages (from-to)393-409
Number of pages17
JournalNeurotoxicity Research
Volume18
Issue number3-4
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Fingerprint

AMPA Receptors
Nucleus Accumbens
Cocaine
Dopamine
Neurons
Cocaine-Related Disorders
Pharmaceutical Preparations
Recurrence
Dopamine D1 Receptors
Neuronal Plasticity
Aptitude
Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Synapses
Cues
Glutamic Acid
Dopamine Receptors
Animal Models
Learning
Plasticity

Keywords

  • Addiction
  • AMPA receptor
  • Dopamine
  • Glutamate
  • Nucleus accumbens
  • Receptor trafficking
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Regulation of AMPA receptor trafficking in the nucleus accumbens by dopamine and cocaine. / Wolf, Marina.

In: Neurotoxicity Research, Vol. 18, No. 3-4, 01.11.2010, p. 393-409.

Research output: Contribution to journalReview article

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