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Annotation

González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature . 2008 Mar 6 ; 452(7183):93-7. PubMed Abstract

Comments on Paper and Primary News
Primary News: 5HT and Glutamate Receptors—Unique Complex Linked to Psychosis

Comment by:  Brian Dean
Submitted 20 March 2008 Posted 20 March 2008

Altered receptor dimerization: a new paradigm in the pathology of schizophrenia
Understanding the pathology of complex diseases such as schizophrenia requires the use of the full arsenal at the disposal of medical research. Such an approach has been used to make an exciting new discovery that suggests that abnormal dimerization between the serotonin 2A receptor (2AR) and the metabotropic glutamate 2 receptor(mGluR2) may underlie some of the symptoms of schizophrenia (González-Maeso et al., 2008).

This discovery is based on an initial finding that 2AR is coexpressed with mGluR2 in layer 5 of the mouse somatosensory cortex (SCx) and that levels of mGluR2 were decreased in the cortex of 2AR-/- mice, suggesting a relationship between the expression of the two genes. This hypothesis was further supported by data showing that expression of mGluR2 was selectively restored in mice where 2AR expression had been re-established in layer 5 of the SCx. From these data, and data from other studies suggesting G protein-coupled...  Read more


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Primary News: 5HT and Glutamate Receptors—Unique Complex Linked to Psychosis

Comment by:  Gerard J. Marek (Disclosure)
Submitted 21 March 2008 Posted 21 March 2008

Another bicycle trip?
Ever since dopamine was first implicated in the therapeutic effects of antipsychotic drugs by Arvid Carlsson and colleagues over 50 years ago, and then dopamine D2 receptors were implicated in the Parkinsonian side effects and late-evolving movement disorders, an intense search has been underway for antipsychotic drugs that might act through other mechanisms. In parallel with this search, drugs with psychotomimetic effects in healthy volunteers or exacerbating psychosis have also been used to discover new antipsychotic drugs. With an evolving understanding of the neuropharmacology underlying ketamine or PCP, amphetamines, and serotonergic hallucinogens (LSD, mescaline, and psilocybin), glutamatergic, dopaminergic, and serotonergic theories of psychotic pathophysiology have been advanced. Converging evidence points to activation of 5-HT2A receptors as a necessary action in the psychotomimetic effects of the serotonergic “hallucinogens.” The recent description of a proof-of-concept clinical study where a prodrug for a metabotropic glutamate2/3...  Read more


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