González-Maeso, J. et al. (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature, 452(7183), pp. 93-97. (doi: 10.1038/nature06612)
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Publisher's URL: http://dx.doi.org/10.1038/nature06612
Abstract
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception.Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of hallucinogenic drugs, such as psilocybin and lysergic acid diethylamide, require the 2AR and resemble some of the core symptoms of schizophrenia. Here we show that the mGluR2 interacts through specific transmembrane helix domains with the 2AR, a member of an unrelated G-protein-coupled receptor family, to form functional complexes in brain cortex. The 2AR-mGluR2 complex triggers unique cellular responses when targeted by hallucinogenic drugs, and activation of mGluR2 abolishes hallucinogen-specific signalling and behavioural responses. In post-mortem human brain from untreated schizophrenic subjects, the 2AR is upregulated and the mGluR2 is downregulated, a pattern that could predispose to psychosis. These regulatory changes indicate that the 2AR-mGluR2 complex may be involved in the altered cortical processes of schizophrenia, and this complex is therefore a promising new target for the treatment of psychosis.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Lopez-Gimenez, Dr Juan and Milligan, Professor Graeme |
| Authors: | González-Maeso, J., Ang, R. L., Yuen, T., Chan, P., Weisstaub, N. V., Lopez-Gimenez, J. F., Zhou, M., Okawa, Y., Callado, L. F., Milligan, G., Gingrich, J. A., Filizola, M., Meana, J. J., and Sealfon, S. C. |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Nature |
| Publisher: | Nature Publishing Group |
| ISSN: | 0028-0836 |
| ISSN (Online): | 1476-4687 |
| Published Online: | 24 February 2008 |
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