5-HT2A-mGluR2

2023-09-08:

5-HT2A-mGluR2 Heteromer #

• Many psychedelics, and perhaps only psychedelics, including LSD bind to mGluR2-5-HT2A heteromers in the frontal lobe (and not 5-HT2A monomers). Serotonin binding only agonizes 5-HT2A, but psychedelics agonize 5-HT2A and inhibit the mGluR2.
• mGluR2/mGluR3 antagonism/KO mice prevents 5-HT2A mediated psychedelic effects: Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists
• Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex
  • 5-HT2A blockade interferes with the induction of BDNF mRNA by stress.
  • Activation of mGlu2/3 receptors suppresses 5-HT2A receptor-stimulated excitatory postsynaptic potentials/currents (EPSP/Cs) in pyramidal neurons in medial prefrontal cortex. Conversely, blockade of mGlu2/3 receptors enhances 5-HT-induced EPSCs.
• AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes
  • Activating 5-HT2A-mGluR2 heteromers effectively antagonizes mGluR2 - not that it’s Gi so this disinhibits glutamate release