Psychomotor stimulants and neuronal plasticity

Marina Wolf, Xiu Sun, Simona Mangiavacchi, Steven Z. Chao

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

Considerable evidence suggests that neuroadaptations leading to addiction involve the same glutamate-dependent cellular mechanisms that enable learning and memory. Long-term potentiation (LTP) and long-term depression (LTD) have therefore become an important focus of addiction research. This article reviews: (1) basic mechanisms underlying LTP and LTD, (2) the properties of LTP and LTD in ventral tegmental area, nucleus accumbens, dorsal striatum and prefrontal cortex, (3) studies demonstrating that psychomotor stimulants influence LTP or LTD in these brain regions. In addition, we discuss our recent work on cellular mechanisms by which dopamine may influence LTP and LTD. Based on evidence that AMPA receptors are inserted into synapses during LTP and removed during LTD, we investigated the effects of D1 receptor stimulation on AMPA receptor trafficking using primary cultures prepared from nucleus accumbens and prefrontal cortex. Our results suggest that activation of the D1 receptor-protein kinase A signaling pathway leads to externalization of AMPA receptors and promotes LTP. This provides a mechanism to explain facilitation of reward-related learning by dopamine. When this mechanism is activated in an unregulated manner by psychostimulants, maladaptive forms of neuroplasticity may occur that contribute to the transition from casual to compulsive drug use.

Original languageEnglish (US)
Pages (from-to)61-79
Number of pages19
JournalNeuropharmacology
Volume47
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

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Keywords

  • AMPA receptor trafficking
  • D1 dopamine receptors
  • Long-term depression
  • Long-term potentiation
  • Nucleus accumbens
  • Prefrontal cortex

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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