Regulation of drug reward by cAMP response element-binding protein

Evidence for two functionally distinct subregions of the ventral tegmental area

Valerie G. Olson, Cyrus P. Zabetian, Carlos A. Bolanos, Scott Edwards, Michel Barrot, Amelia J. Eisch, Thomas Hughes, David W. Self, Rachael L. Neve, Eric J. Nestler

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

The transcription factor cAMP response element binding protein (CREB) is implicated in the actions of drugs of abuse in several brain areas, but little information is available about a role for CREB in the ventral tegmental area (VTA), one of the key reward regions of the brain. Here, we demonstrate that chronic exposure to drugs of abuse induces CREB activity throughout the VTA. Using viral-mediated gene transfer, we expressed green fluorescent protein (GFP)-tagged CREB or mCREB (a dominant-negative form of CREB) in the VTA and, using a conditioned place-preference paradigm, found that CREB activation within the rostral versus caudal subregions of the VTA produces opposite effects on drug reward. We identified VTA subregion-specific differences in the proportion of dopaminergic and GABAergic neurons and in the dopaminergic projections to the nucleus accumbens, another brain region implicated in drug reward, and suggest that this may contribute to behavioral differences in this study. We also measured expression levels of tyrosine hydroxylase and the AMPA glutamate receptor subunit GluR1, both of which are known to contribute to drug reward in the VTA, and found that both of these genes are upregulated following the expression of CREB-GFP and downregulated following expression of mCREB-GFP, raising the possibility that CREB may exert its effects on drug reward, in part, via regulation of these genes. These results suggest a novel role for CREB in mediating drug-induced plasticity in the VTA and establish two functionally distinct subregions of the VTA in which CREB differentially regulates drug reward.

Original languageEnglish (US)
Pages (from-to)5553-5562
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number23
DOIs
StatePublished - Jun 8 2005

Fingerprint

Cyclic AMP Response Element-Binding Protein
Ventral Tegmental Area
Drug and Narcotic Control
Reward
Green Fluorescent Proteins
Pharmaceutical Preparations
Street Drugs
Brain
GABAergic Neurons
AMPA Receptors
Viral Genes
Dopaminergic Neurons
Nucleus Accumbens
Glutamate Receptors
Tyrosine 3-Monooxygenase
Genes
Transcription Factors
Down-Regulation

Keywords

  • Cocaine
  • CREB
  • Mesocortical
  • Mesolimbic
  • Morphine
  • Reward
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of drug reward by cAMP response element-binding protein : Evidence for two functionally distinct subregions of the ventral tegmental area. / Olson, Valerie G.; Zabetian, Cyrus P.; Bolanos, Carlos A.; Edwards, Scott; Barrot, Michel; Eisch, Amelia J.; Hughes, Thomas; Self, David W.; Neve, Rachael L.; Nestler, Eric J.

In: Journal of Neuroscience, Vol. 25, No. 23, 08.06.2005, p. 5553-5562.

Research output: Contribution to journalArticle

Olson, Valerie G. ; Zabetian, Cyrus P. ; Bolanos, Carlos A. ; Edwards, Scott ; Barrot, Michel ; Eisch, Amelia J. ; Hughes, Thomas ; Self, David W. ; Neve, Rachael L. ; Nestler, Eric J. / Regulation of drug reward by cAMP response element-binding protein : Evidence for two functionally distinct subregions of the ventral tegmental area. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 23. pp. 5553-5562.
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KW - Cocaine

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