Pharmacological stimulation of NMDA receptors via co-agonist site suppresses fMRI response to phencyclidine in the rat.
Psychopharmacology December 1, 2008 Alessandro Gozzi, Hugh Herdon, Adam Schwarz et al.
Impaired NMDA receptor function may underlie schizophrenia. Drugs that activate the glycine binding site of the NMDA receptor could boost its activity and offer therapeutic benefit. In rats, the NMDA antagonist PCP activated brain circuits involved in schizophrenia. Pretreatment with D-serine (1 g/kg) or the GlyT-1 inhibitor SSR504734 (10 mg/kg) completely blocked this activation and caused weak, sustained deactivation in cortical areas. The results suggest that agents acting at the glycine co-agonist site can enhance NMDA receptor activity in the living brain and support their potential for treating schizophrenia.