New OCD suppression target

Abstract

Obsessive-compulsive disorder (OCD) is a disabling psychiatric condition affecting up to 3% of the population, marked by intrusive thoughts and compulsive behaviors. Current treatments, such as selective serotonin reuptake inhibitors, are not universally effective. OCD pathology is linked to hyperactivity in corticostriatal-thalamic circuits and elevated glutamate:GABA ratios in brain regions like the anterior cingulate cortex. A study in Psychopharmacology analyzes the potential of targeting glutamatergic signaling via metabotropic glutamate receptors to reduce compulsive behaviors in male Lister-Hooded rats. Using the Observing Response Task after categorizing rats into groups that mimic OCD-like checking behavior, characterized by repetitive actions, researchers tested two compounds: the metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator AZD-8529 and the mGluR2/3 agonist LY404039 (pomaglumetad). Both drugs dose-dependently reduced excessive checking without impairing reward-seeking behavior or cue-guided responses when compared with vehicle-treated animals. These findings indicate that mGluR2-targeting compounds can selectively and safely suppress compulsive-like checking, highlighting a promising new therapeutic avenue. This work supports further research of glutamatergic modulation in treating OCD, offering potential future treatment for patients unresponsive to conventional therapies.

Original reference: McKenzie, C. et al. Psychopharmacology (2025). https://doi.org/10.1007/s00213-025-06774-2