Fig. 5.

Pharmacological strategies to target the 5-HT_2AR-mGluR2 complex. Potential routes to affect the crosstalk between 5-HT_2AR and mGluR2 include i) HDAC2 inhibitors to prevent the 5-HT_2AR-dependent epigenetic modifications at the mGluR2 promoter upon chronic antipsychotic treatment, ii) orthosteric and allosteric mGluR2 agonists as antipsychotics, iii) classical psychedelics as fast-acting antidepressants, and iv) bivalent ligands composed of 5-HT_2AR antagonists and mGluR2 PAMs as a pharmacological tool to treat schizophrenia.