The effects of glycine transporter I inhibitor, N-methylglycine (sarcosine), on ketamine-induced alterations in sensorimotor gating and regional brain c-Fos expression in rats.
Reduced N-methyl-D-aspartate receptor (NMDAR) function may contribute to the pathogenesis of schizophrenia. Sarcosine, a potent glycine transporter inhibitor, can increase synaptic glycine and then promote NMDAR function. We assessed the antipsychotic potential of sarcosine by comparing the abilities of sarcosine and clozapine to restore the prepulse inhibition (PPI) deficit, hyperlocomotion and regional brain c-Fos expression changes caused by an NMDAR antagonist, ketamine. Four groups of rats were given acute injections, including saline+saline, saline+30 mg/kg ketamine, 100mg/kg sarcosine+30 mg/kg ketamine, and 15 mg/kg clozapine+30 mg/kg ketamine. Both sarcosine and clozapine reversed the ketamine-induced PPI deficit and hyperlocomotion. They both did not change ketamine-induced increase in c-Fos expression in the prefrontal cortex and nucleus accumbens. However, in the olfactory bulb, sarcosine, but not clozapine, significantly reduced the ketamine-induced increase in c-Fos expression. Our animal study demonstrated that sarcosine may have antipsychotic potential.
Yang
Shii-Yi
SY
Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
Hong
Chen-Jee
CJ
Huang
Yn-Ho
YH
Tsai
Shih-Jen
SJ
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007649:Ketamine; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects; D012521:Sarcosine / Q000494:pharmacology*; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*
D014150:Antipsychotic Agents; D050487:Glycine Plasma Membrane Transport Proteins; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; C493266:Slc6a9 protein, rat; D007649:Ketamine; D012521:Sarcosine