A single high dose of cocaine induces behavioural sensitization and modifies mRNA encoding GluR1 and GAP-43 in rats

Giuliano Grignaschi, Silvia Burbassi, Eleonora Zennaro, Caterina Bendotti, Luigi Cervo

Research output: Contribution to journalArticle

Abstract

Neuroadaptive changes underlying repeated exposure to cocaine-induced behavioural sensitization have been related to modification in the pattern of synaptic connectivity and excitatory transmission. Remarkably, even a single exposure to abused drugs is sufficient to elicit lasting behavioural sensitization. The present study investigated whether in Sprague-Dawley rats a single, behavioural sensitizing dose of cocaine is sufficient to induce changes in the mRNA levels of growth-associated protein 43 (GAP-43), an important protein in mediating experience-dependent plasticity and synaptic reorganization, and of glutamate receptor 1 (GluR1), a subunit of AMPA glutamate receptors, a protein that is up-regulated with repeated cocaine. Single exposure to 20, but not 10 mg/kg cocaine induced locomotor sensitization to a second injection of 10 mg/kg cocaine, observed at 24 h, 48 h and 7 days. Single dose of 20 but not 10 mg/kg cocaine 48 h before scheduled death significantly enhanced GluR1 and GAP-43 mRNA expression in the nucleus accumbens (NAc), both shell and core subregions, and ventral tegmental area (VTA). No changes were found in the levels of mRNA for GluR1 and GAP-43 in the frontal cortex, caudate putamen, dentate gyrus of hippocampus and basolateral nucleus of the amygdala after the single dose of 20 mg/kg cocaine. These results further strengthen the involvement of NAc and VTA in the behavioural sensitization and suggest a role of GAP-43 in the synaptic reorganization associated to drug abuse.

Original languageEnglish
Pages (from-to)2833-2837
Number of pages5
JournalEuropean Journal of Neuroscience
Volume20
Issue number10
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Cocaine
  • GAP-43
  • Locomotor sensitization
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

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