In vivo evidence that genetic background controls impulse-dependent dopamine release induced by amphetamine in the nucleus accumbens

Rossella Ventura, Antonio Alcaro, Laura Mandolesi, Stefano Puglisi-Allegra

Research output: Contribution to journalArticlepeer-review

Abstract

Amphetamine is known to increase dopamine (DA) release by acting directly on dopamine transporters (DAT), primarily through a mechanism that is independent of impulse flow. We present evidence to show that impulse-dependent increase in DA outflow in the nucleus accumbens (NAc) is produced by amphetamine depending on genetic background. Systemic amphetamine produced higher accumbal DA release in the widely exploited C57BL/6J background than in the DBA/2J. By contrast, intra-accumbens perfusion using increasing doses of amphetamine dramatically increased DA outflow in the DBA/2J background, whereas very low DA outflow was evident in C57BL/6J mice. The fast sodium channel blocker tetrodotoxin infused through the microdialysis probe abolished accumbal DA release induced by systemic amphetamine only in the C57BL/6J background. Finally, medial prefrontal excitotoxic lesion abolished amphetamine-induced mesoaccumbens DA release in C57BL/6J mice, without significantly affecting it in the DBA/2J background. These results represent the first functional evidence in an in vivo study that amphetamine can increase DA release in the NAc mainly through an impulse-dependent mechanism regulated by prefronto-cortical glutamatergic transmission. Moreover, they point to a genetic control of impulse-dependent DA release in the accumbens, providing an exploitable tool to investigate aetiological factors involved in psychopathology and drug addiction.

Original languageEnglish
Pages (from-to)494-502
Number of pages9
JournalJournal of Neurochemistry
Volume89
Issue number2
DOIs
Publication statusPublished - Apr 2004

Keywords

  • D-amphetamine
  • Dopamine
  • Genotype
  • Glutamate
  • Nucleus accumbens
  • Prefrontal cortex

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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