Psychopharmacology

, Volume 197, Issue 2, pp 179–189

Repeated amphetamine administration induces Fos in prefrontal cortical neurons that project to the lateral hypothalamus but not the nucleus accumbens or basolateral amygdala

Original Investigation

DOI: 10.1007/s00213-007-1021-7

Cite this article as:
Morshedi, M.M. & Meredith, G.E. Psychopharmacology (2008) 197: 179. doi:10.1007/s00213-007-1021-7

Abstract

Rationale

The development of sensitization to amphetamine (AMPH) is dependent on increases in excitatory outflow from the medial prefrontal cortex (mPFC) to subcortical centers. These projections are clearly important for the progressive enhancement of the behavioral response during drug administration that persists through withdrawal.

Objectives

The objective of this study was to identify the mPFC subcortical pathway(s) activated by a sensitizing regimen of AMPH.

Materials and methods

Using retrograde labeling techniques, Fos activation was evaluated in the predominant projection pathways of the mPFC of sensitized rats after a challenge injection of AMPH.

Results

There was a significant increase in Fos-immunoreactive cells in the mPFC, nucleus accumbens (NAc), basolateral amygdala (BLA), and lateral hypothalamus (LH) of rats treated repeatedly with AMPH when compared to vehicle-treated controls. The mPFC pyramidal neurons that project to the LH but not the NAc or BLA show a significant induction of Fos after repeated AMPH treatment. In addition, we found a dramatic increase in Fos-activated orexin neurons.

Conclusions

The LH, a region implicated in natural and drug reward processes, may play a role in the development and persistence of sensitization to repeated AMPH through its connections with the mPFC and possibly through its orexin neurons.

Keywords

DopaminePsychostimulantBehavioral sensitizationPrelimbic cortexInfralimbic cortexRewardAddictionFluoro-goldOrexin

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Cellular and Molecular Pharmacology, Chicago Medical SchoolRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA