Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release

Rossella Ventura, Simona Cabib, Antonio Alcaro, Cristina Orsini, Stefano Puglisi-Allegra

Research output: Contribution to journalArticlepeer-review


Increasing evidence points to a major involvement of cortical areas in addictive mechanisms. Noradrenergic transmission in the medial prefrontal cortex (mpFC) has been shown to affect the motor effects of amphetamine, although there is no evidence of its involvement in the rewarding effects of this psychostimulant. The present experiments were aimed at investigating the possibility of a selective involvement of prefrontal cortical norepinephrine (NE) in the rewarding-reinforcing effects of amphetamine. To do so, we evaluated the effects of mpFC NE selective depletion in mice of C57BL/6J inbred strain, a background commonly used in molecular approaches that is known to be highly susceptible to the rewarding effects of the psychostimulant. In a first set of experiments, we demonstrated the absence of amphetamine-induced conditioned place preference in mice bearing prefrontal NE depletion. In a second series of experiments, we demonstrated that the same lesion dramatically reduced amphetamine-induced mesoaccumbens dopamine release as measured by intracerebral microdialysis. These results indicate that noradrenergic prefrontal transmission, by allowing increased dopamine release in the nucleus accumbens induced by amphetamine, is a critical factor for the rewarding-reinforcing effects of this drug.

Original languageEnglish
Pages (from-to)1879-1885
Number of pages7
JournalJournal of Neuroscience
Issue number5
Publication statusPublished - Mar 1 2003


  • Conditioned place preference
  • Dopamine
  • Norepinephrine
  • Nucleus accumbens
  • Prefrontal cortex
  • Reward

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Norepinephrine in the prefrontal cortex is critical for amphetamine-induced reward and mesoaccumbens dopamine release'. Together they form a unique fingerprint.

Cite this