Cited by 186Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeural and Behavioral Psychology Studies

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Regulation of Drug Reward by cAMP Response Element-Binding Protein: Evidence for Two Functionally Distinct Subregions of the Ventral Tegmental Area

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Olson, V. G.·2005·Journal of Neuroscience

DOI 10.1523/jneurosci.0345-05.2005PMC PMC6724971

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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.

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Authors: Olson, V. G.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Olson, V. G.
ORCID: Olson, V. G.
Venue: Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2005-06-08
Volume: 25
Issue: 23
Pages: 5553-5562
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0345-05.2005
PMC: PMC6724971
OpenAlex: W2092206787
Cited by: 186
References: 63
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 4 · 2018: 8 · 2017: 10 · 2016: 4 · 2015: 7 · 2014: 8 · 2013: 15 · 2012: 13
FWCI: 6.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institute of Mental Health
National Institute on Drug Abuse
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: CREB, drug reward, ventral tegmental area, drugs of abuse, conditioned place preference, dominant-negative CREB, dopaminergic neurons, GABAergic neurons, tyrosine hydroxylase, transcriptional regulation
MeSH terms: Animals, Behavior, Animal, Cocaine, Conditioning, Psychological, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Morphine, Narcotics, Neurons, Nucleus Accumbens, Recombinant Fusion Proteins, Reward, Transcription, Genetic, Tyrosine 3-Monooxygenase, Up-Regulation, Cyclic AMP Response Element-Binding Protein, Ventral Tegmental Area, Receptors, AMPA, Green Fluorescent Proteins, Mice

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Regulation of Drug Reward by cAMP Response Element-Binding Protein: Evidence for Two Functionally Distinct Subregions of the Ventral Tegmental Area

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