The International Journal of Neuropsychopharmacology

Research Article

CREB-mediated alterations in the amygdala transcriptome: coordinated regulation of immune response genes following cocaine

Laurel E. Eckea1, Jessica N. Clecka1, Peter Whitea2, Jonathan Schuga2, Lauren Mifflina1 and Julie A. Blendya1 c1

a1 Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

a2 Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

Abstract

The neuronal circuitry underlying stress- and drug-induced reinstatement of cocaine-seeking has been relatively well characterized; however, less is known regarding the long-term molecular changes following cocaine administration that may promote future reinstatement. The transcription factor cAMP response element-binding protein (CREB) is necessary for stress- but not cocaine-induced reinstatement of conditioned reward, suggesting that different molecular mechanisms may underlie these two types of reinstatement. To explore the relationship between this transcription factor and reinstatement, we utilized the place-conditioning paradigm to examine alterations in gene expression in the amygdala, a neural substrate critically involved in stress-induced reinstatement, following the development of cocaine reward and subsequent extinction. Our findings demonstrate that the amygdala transcriptome was altered by CREB deficiency more than by previous cocaine experience, with an over-representation of genes involved in the immune response. However, a subset of genes involved in stress and immune response demonstrated a drug×genotype interaction, indicating that cocaine produces different long-term alterations in gene expression depending on the presence or absence of CREB. This profile of gene expression in the context of addiction enhances our understanding of the long-term molecular changes that occur throughout the addiction cycle and identifies novel genes and pathways that might lead to the creation of better therapeutic agents.

(Received August 11 2010)

(Reviewed September 24 2010)

(Revised October 14 2010)

(Accepted October 26 2010)

(Online publication December 08 2010)

Correspondence:

c1 Address for correspondence: J. A. Blendy, Ph.D., Department of Pharmacology, Center for Neurobiology and Behavior, Translational Research Laboratories, 125 S. 31st St, Philadelphia, PA 19104-3403, USA. Tel.: 215-898-0730 Fax: 215-573-2041 Email: blendy@mail.med.upenn.edu

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