Frustrated expected reward induces differential transcriptional changes in the mouse brain: Microarrays and frustration
Open accessAbstract
Frustration represents a particular aspect of the addictive process that is related to loss of control when the expected reward is not obtained. We aim to study the consequences of frustrated expected reward on gene expression in the mouse brain. For this purpose, we used an operant model of frustration using palatable food as reward combined with microarrays. Transcriptomic profiles of frontal cortex, ventral striatum and hippocampus were analysed in five groups of mice: (1) positive control receiving palatable food and the cue light as conditioned stimulus; (2) frustrated group only receiving the cue light; (3) extinction learning group that did not receive palatable food nor the light; (4) negative control that never received the reinforcer nor the light during the whole experiment; and (5) yoked that received palatable food passively. Gene expression changes produced by frustration were revealed in the frontal cortex and ventral striatum, but not in the hippocampus. Most of the changes, such as the modification of the dopamine-DARPP-32 signalling pathway, were common in both areas and estimated to have neuronal origin. Extinction learning induced transcriptional changes only in the ventral striatum, with most genes showing down-regulation and without alteration in the dopamine-DARPP-32 signalling pathway. Active palatable food-seeking behaviour induced changes in gene expression in ventral striatum mainly affecting cell communication. In conclusion, frustration behaviour-induced changes in frontal cortex and ventral striatum mainly related to dopamine-DARPP-32 signalling that could play an important role in the loss of behavioural control during the addictive processes.
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The downregulation of dopamine-DARPP32 feedback in cAMP signaling was also found altered in the ventral striatum and the frontal cortex of an operant mouse model of frustration showing aggressive behavior.
“The only consistent directional change of these shared pathways between the two rodent models, the downregulation of the dopamine-DARPP32 feedback in cAMP signaling, was also found altered in the ventral striatum and the frontal cortex of an operant mouse model of frustration showing aggressive behavior [63].”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [63]
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- Authors
- Martín-García, E., Fernández-Castillo, N., Burokas, A., Gutiérrez-Cuesta, J., Sánchez-Mora, C., Casas, M., Ribasés, M., Cormand, B., & Maldonado, R.
- Affiliations
- Laboratori de Neurofarmacologia; Departament de Ciències Experimentals i de la Salut; PRBB; Universitat Pompeu Fabra; Spain
- Departament de Genètica; Facultat de Biologia; Universitat de Barcelona; Spain
- Universitat Pompeu Fabra (ES)
- Department of Psychiatry; Hospital Universitari Vall d'Hebron; Spain
- Universitat Autònoma de Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Maldonado, Rafael
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2014-10-06
- Volume
- 20
- Issue
- 1
- Pages
- 22-37
- ISSN
- 1355-6215 (ISSN-L)
- OpenAlex
- W2163818839
- Cited by
- 16
- References
- 46
- Citations by year
- 2025: 1 · 2024: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 1
- FWCI
- 0.61
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion, other-oa)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion)
- Funders
- Generalitat de Catalunya (2009-SGR-00131 and 2014-SGR-0932)
- European Commission (FP7/2007– 2013 grant agreement n° 602805)
- ICREA Fundation (ICREA Academia 2008)
- Instituto de Salud Carlos III (RTA, RD06/001/001, RTA, PI11/01629)
- Ministerio de Sanidad y PolÃtica Social (PNSD 2009/022 and 2099/026)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Keywords
- frustration, expected reward, gene expression, brain transcriptome, frontal cortex, ventral striatum, hippocampus, extinction learning, operant conditioning, loss of control, addiction, intercellular communication
- MeSH terms
- Homeobox Protein Nkx-2.5, Animals, Brain, Conditioning, Operant, Food, Frontal Lobe, Frustration, Hippocampus, Male, Reward, RNA, Messenger, Transcription Factors, Signal Transduction, Trans-Activators, Gene Expression, Homeodomain Proteins, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Mice, Sex-Determining Region Y Protein, Dopamine and cAMP-Regulated Phosphoprotein 32, SOXD Transcription Factors, Transcriptome, Ventral Striatum
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