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ΔFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment

Perrotti, Linda I., Bolaños, Carlos A., Choi, Kwang‐Ho, Russo, Scott J., Edwards, Scott, Ulery, Paula G., Wallace, Deanna L., Self, David W., Nestler, Eric J., Barrot, Michel·2005·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2005.04110.x

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Abstract

The transcription factor deltaFosB is induced in the nucleus accumbens and dorsal striatum by chronic exposure to several drugs of abuse, and increasing evidence supports the possibility that this induction is involved in the addiction process. However, to date there has been no report of deltaFosB induction by drugs of abuse in the ventral tegmental area (VTA), which is also a critical brain reward region. In the present study, we used immunohistochemistry to demonstrate that chronic forced administration of cocaine induces deltaFosB in the rat VTA. This induction occurs selectively in a gamma-aminobutyric acid (GABA) cell population within the posterior tail of the VTA. A similar effect is seen after chronic cocaine self-administration. Induction of deltaFosB in the VTA occurs after psychostimulant treatment only: it is seen with both chronic cocaine and amphetamine, but not with chronic opiates or stress. The expression of deltaFosB appears to be mediated by dopamine systems, as repeated administration of a dopamine uptake inhibitor induced deltaFosB in the VTA, while administration of serotonin or norepinephrine uptake inhibitors failed to produce this effect. Time course analysis showed that, following 14 days of cocaine administration, deltaFosB persists in the VTA for almost 2 weeks after cocaine withdrawal. This accumulation and persistence may account for some of the long-lasting changes in the brain associated with chronic drug use. These results provide the first evidence of deltaFosB induction in a discrete population of GABA cells in the VTA, which may regulate the functioning of the brain's reward mechanisms.

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Background
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Background
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Background
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Background
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Background
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Late expression of FosB transcription factor in 4-aminopyridine-induced seizures in the rat cerebral cortex
Bagosi, A., Bakos, M., Krisztin‐Péva, B., & Mihály, A. (2008) · Acta Histochemica · doi:10.1016/j.acthis.2007.12.001 · Cited by 1
“Since antibodies selective for DFosB are not available, we used a rabbit polyclonal antiserum raised against an internal region of FosB (sc-48; Santa Cruz Biotechnology), that has been shown to recognize both FosB and DFosB (Perotti et al., 2005).”
Method
Comparison of ethanol-related behaviors and FosB mapping in hybrid mice with distinct drinking patterns
Ozburn, A. R. (2009) · Texas ScholarWorks (Texas Digital Library)
Role of the Ventral Tegmental Area and Ventral Tegmental Area Nicotinic Acetylcholine Receptors in the Incentive Amplifying Effect of Nicotine
Sheppard, A. B. (2014) · Digital Commons - East Tennessee State University (East Tennessee State University)
Differential gene expression in acute and chronic seizure models in the rat brain
Bagosi, A. (2008)
"AFERÊNCIAS HIPOTALÂMICAS PARA A ÁREA TEGMENTAL VENTRAL, NÚCLEO TEGMENTAL ROSTROMEDIAL E NÚCLEO DORSAL DA RAFE."
Humana, E. F., & Andreas, M. (2015)
Exploring Sex Differences In Psychostimulant-induced Activation Of The Tail Of The Ventral Tegmental Area
Dennis, T. S. (2014) · UTA ResearchCommons (University of Texas Arlington)
The effect of MDMA self-administration on MDMA-produced hyperactivity and c-fos expression
Bukholt, N. (2016) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.17018618
The Role of VTA Gabaergic Nicotinic Acetylcholine Receptors Containing the α4 Subunit in Nicotine Dependence: A Dissertation
Ngolab, J. (2015) · The Journal of the American Medical Association (JAMA) Network (American Medical Association) · doi:10.13028/m2730b
“It is interesting to note that psychostimulants activate the RMTg as determined by Fos immunoreactivity (Perrotti et al., 2005), for it suggests inhibitory input into the VTA contributes to the rewarding effects of these drugs.”
BackgroundInfluential
Effect of repeated MDMA exposure on rat brain and behaviour
van de Wetering, R. (2020) · Figshare · doi:10.26686/wgtn.17148296.v1
The rostromedial tegmental nucleus: Features and links with alcohol and depression
Zuo, Q., Zuo, W., Eloy, J. D., & Ye, J.-H. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817935-2.00031-3
Effect of repeated MDMA exposure on rat brain and behaviour
van de Wetering, R. (2020) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.17148296
Faculty Opinions recommendation of One is not enough: understanding and modeling polysubstance use.
Grunberg, N. E. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738149771.793576347
Literature cited
(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15596-3.16001-1
eLife Assessment: Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses
Day, J. J. (2024) · eLife · doi:10.7554/elife.100085.1.sa3
Reviewer #3 (Public Review): Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses
Oriol, L., Chao, M., Kollman, G. J., et al. (2024) · eLife · doi:10.7554/elife.100085.1.sa0
Reviewer #1 (Public Review): : Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses
Oriol, L., Chao, M., Kollman, G. J., et al. (2024) · eLife · doi:10.7554/elife.100085.1.sa2
Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapsesPreprint
Oriol, L., Chao, M., Kollman, G. J., Dowlat, D. S., Singhal, S. M., Steinkellner, T., & Hnasko, T. S. (2025) · eLife · doi:10.7554/elife.100085.2
Neuroplasticity in the Mesolimbic System Induced by Sexual Experience and Subsequent Reward Abstinence
Pitchers, K. K. (2012) · Scholarship@Western (Western University)
Transcription Factors ∆FosB and CREB in Drug Addiction : Studies in Models of Alcohol Preference and Chronic Nicotine Exposure
Kaste, K. (2009) · Työväentutkimus Vuosikirja
Caractérisation des circuits neuronaux contrôlant l’activité des neurones dopaminergiques de l’aire tegmentale ventrale
Jalabert, M. (2011) · theses.fr (ABES) · doi:10.70675/4d4ba3a7zce38z40f7za8adz84111f198b6f
La queue de l’aire tegmentale ventrale : définition anatomo-moléculaire, implication dans la réponse aux stimuli aversifs et influence sur la voie nigrostriée
Faivre, F. (2018) · doi:10.70675/b30f731az3333z44bbz8cb6za26c36c3c9a8

Authors: Perrotti, L. I., Bolaños, C. A., Choi, K., Russo, S. J., Edwards, S., Ulery, P. G., Wallace, D. L., Self, D. W., Nestler, E. J., & Barrot, M.
Affiliations: The University of Texas Southwestern Medical Center (US)
Florida State University (US)
Centre National de la Recherche Scientifique (FR)
ORCID: Perrotti, Linda I.
Choi, Kwang‐Ho
Russo, Scott J.
Edwards, Scott
Wallace, Deanna L.
Self, David W.
Nestler, Eric J.
Barrot, Michel
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2005-05
Volume: 21
Issue: 10
Pages: 2817-2824
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2005.04110.x
OpenAlex: W1967616722
Cited by: 178
References: 61
Citations by year: 2025: 3 · 2024: 10 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 5 · 2017: 5 · 2016: 17 · 2015: 9 · 2014: 14 · 2013: 9 · 2012: 14
FWCI: 3.14
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 26 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: ΔFosB, ventral tegmental area, GABAergic neurons, cocaine, amphetamine, psychostimulants, drug addiction, dopamine, brain reward, cocaine self-administration, cocaine withdrawal, chronic drug exposure, transcription factor induction
MeSH terms: Animals, Cocaine, gamma-Aminobutyric Acid, Kinetics, Male, Morphine, Self Administration, Transcription Factors, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Ventral Tegmental Area, Cocaine-Related Disorders, Rats

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ΔFosB accumulates in a GABAergic cell population in the posterior tail of the ventral tegmental area after psychostimulant treatment

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