Dysfunctional heteroreceptor complexes as novel targets for the treatment of major depressive and anxiety disorders
Open accessAbstract
Among mental diseases, major depressive disorder (MDD) and anxiety deserve a special place due to their high prevalence and their negative impact both on society and patients suffering from these disorders. Consequently, the development of novel strategies designed to treat them quickly and efficiently, without or at least having limited side effects, is considered a highly important goal. Growing evidence indicates that emerging properties are developed on recognition, trafficking, and signaling of G-protein coupled receptors (GPCRs) upon their heteromerization with other types of GPCRs, receptor tyrosine kinases, and ionotropic receptors such as N-methyl-D-aspartate (NMDA) receptors. Therefore, to develop new treatments for MDD and anxiety, it will be important to identify the most vulnerable heteroreceptor complexes involved in MDD and anxiety. This review focuses on how GPCRs, especially serotonin, dopamine, galanin, and opioid heteroreceptor complexes, modulate synaptic and volume transmission in the limbic networks of the brain. We attempt to provide information showing how these emerging concepts can contribute to finding new ways to treat both MDD and anxiety disorders.
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The OXTR has a dependence on allosteric modulators like cholesterol and magnesium (Mg2+) for full activation.
“It is of interest that the OXTR has a dependence on allosteric modulators like cholesterol and magnesium (Mg2+) for full activation (Klein et al., 1995a,b; Perez de la Mora et al., 2022).”
From The oxytocin receptor represents a key hub in the GPCR heteroreceptor network: Potential relevance for brain and behavior (2022) · cites this paper as Perez de la Mora et al., 2022
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Guarraci, F. A., Frohardt, R. J., Falls, W. A., & Kapp, B. S. (2000) · Behavioral Neuroscience · doi:10.1037//0735-7044.114.3.647 · Cited by 140 · see citing works
Reversal of Depressed Behaviors in Mice by p11 Gene Therapy in the Nucleus Accumbens
Alexander, B., Warner-Schmidt, J., Eriksson, T. M., Tamminga, C., Arango-Lievano, M., Ghose, S., Vernov, M., Stavarache, M., Musatov, S., Flajolet, M., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3001079 · Cited by 140 · see citing works
Guarraci, F. A., Frohardt, R. J., Falls, W. A., & Kapp, B. S. (2000) · Behavioral Neuroscience · doi:10.1037/0735-7044.114.3.647 · Cited by 140 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [15]Belon J.P. L’anxiété et Les Troubles Anxieux (Anxiety and Anxiety Disorders) Actual. Pharm. 2019 58 18 22 10.1016/J.ACTPHA.2019.09.005 · DOI
- [91]Fuxe K. Agnati L.F. Two Principal Modes of Electrochemical Communication in the Brain: Volume Versus Wiring Transmission Volume Transmission in the Brain: Novel Mechanisms for Neural Transmission Fuxe K. Agnati L.F. Raven Press New York, NY, USA 1991 1 9
- [113]Flores-Burgess A. Millón C. Gago B. Narváez J.A. Fuxe K. Díaz-Cabiale Z. Small Interference RNA Knockdown Rats in Behavior Neuromethods Wolfgang W. Springer Nature Basel, Switzerland 2018 133 148 9781493989447
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Molecular pathways of major depressive disorder converge on the synapse
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Singewald, N., Sartori, S. B., Reif, A., & Holmes, A. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109418 · Cited by 61 · see citing works
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Self-citationFunctional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders
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Han, D., Zhao, Z., Mao, T., Gao, M., Yang, X., & Gao, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70150 · Cited by 30 · see citing works
Mirchandani‐Duque, M., Choucri, M., Hernández-Mondragón, J. C., Crespo‐Ramírez, M., Pérez-Olives, C., Ferraro, L., Franco, R., de la Mora, M. P., Fuxé, K., & Borroto‐Escuela, D. O. (2024) · Membranes · doi:10.3390/membranes14050096 · Cited by 14 · see citing works
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Alia, A. G. M., Hu, X., Gu, Y., Yau, J., Tian, G., Semmelhack, J. L., Saito, K., Tanimoto, H., Tsuyuzaki, K., Naganos, S., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2517987123 · Cited by 1 · see citing works
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- Authors
- Pérez de la Mora, M., Borroto-Escuela, D. O., Crespo-Ramírez, M., Rejón-Orantes, J. D. C., Palacios-Lagunas, D. A., Martínez-Mata, M. K., Sánchez-Luna, D., Tesoro-Cruz, E., & Fuxe, K.
- Affiliations
- Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
- Department of Neuroscience, Karolinska Institutet, Biomedicum, Solnavägen 9., 17177 Stockholm, Sweden
- Universidad Autónoma de Chiapas (MX)
- Universidad Nacional Autónoma de México (MX)
- Mexican Social Security Institute (MX)
- ORCID
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2022-06-02
- Volume
- 11
- Issue
- 11
- Pages
- 1826
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC9180493
- OpenAlex
- W4281758282
- Cited by
- 21
- References
- 393
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Dirección General de Asuntos del Personal Académico (DGAPA) (IN206820, FIS/IMSS/PROT/G14/1320 ET-C, EMERGIA 2020-39318)
- Stiftelsen Olle Engkvist Byggmästare, Stockholm, Sweden, Swedish Medical Research Council (IN206820, FIS/IMSS/PROT/G14/1320 ET-C, EMERGIA 2020-39318)
- Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (IN206820, FIS/IMSS/PROT/G14/1320 ET-C, EMERGIA 2020-39318)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, anxiety disorders, serotonin receptors, dopamine receptors, galanin receptors, opioid receptors, NMDA receptor, synaptic transmission, volume transmission, limbic system, novel therapeutic targets
- MeSH terms
- Anxiety Disorders, Major Depressive Disorder, Humans, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, G-Protein-Coupled
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