Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli

doi:10.1073/pnas.0610178104

Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli

*Santa Lucia Foundation, European Centre for Brain Research (CERC), Via del Fosso di Fiorano 65, 00143 Rome, Italy;
^†Dipartimento di Scienze e Tecnologie Biomediche, Università degli Studi dell'Aquila, Via Vetoio, 67010 Coppito, L'Aquila, Italy; and
^§Dipartimento di Psicologia and Centro “Daniel Bovet,” Università degli Studi di Roma “La Sapienza,” Via dei Marsi 78, 00185 Rome, Italy

Edited by James L. McGaugh, University of California, Irvine, CA, and approved February 5, 2007 (received for review November 16, 2006)

Abstract

Recent evidence suggests that rewarding and aversive stimuli affect the same brain areas, including medial prefrontal cortex and nucleus accumbens. Although nucleus accumbens is known to respond to salient stimuli, regardless of their hedonic valence, with selective increased dopamine release, little is known about the role of prefrontal cortex in reward- and aversion-related motivation or about the neurotransmitters involved. Here we find that selective norepinephrine depletion in medial prefrontal cortex of mice abolished the increase in the release of norepinephrine by prefrontal cortex and of dopamine by nucleus accumbens that is induced by food, cocaine, or lithium chloride and impaired the place conditioning induced by both lithium chloride (aversion) and food or cocaine (preference). This is evidence that prefrontal cortical norepinephrine transmission is necessary for motivational salience attribution to both reward- and aversion-related stimuli through modulation of dopamine in nucleus accumbens, a brain area involved in all motivated behaviors.

Footnotes

^‡To whom correspondence should be addressed. E-mail: rossella.ventura{at}cc.univaq.it
Author contributions: R.V. and S.P.-A. designed research; R.V. and C.M. performed research; R.V., C.M., and S.P.-A. analyzed data; and R.V. and S.P.-A. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Abbreviations:

NAc,

nucleus accumbens;

pFC,

prefrontal cortex;

mpFC,

medial pFC;

CPP,

conditioned place preference;

CPA,

conditioned place aversion;

6-OHDA,

6-hydroxydopamine.
Freely available online through the PNAS open access option.