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

• Published in: Neuroscience letters 2010-01, Vol.469 (1), p.127-130
• Main Authors: Yang, Shii-Yi, Hong, Chen-Jee, Huang, Yn-Ho, Tsai, Shih-Jen
• Format: Article
• Language: English
• Subjects: Animals; Antipsychotic Agents - pharmacology; Biological and medical sciences; c-Fos; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Clozapine; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Glycine Plasma Membrane Transport Proteins - antagonists & inhibitors; Humans; Ketamine; Medical sciences; Motor Activity - drug effects; Neural Inhibition; Neuropharmacology; Pharmacology. Drug treatments; Prepulse inhibition; Proto-Oncogene Proteins c-fos - biosynthesis; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Reflex, Startle - drug effects; Sarcosine; Sarcosine - pharmacology; Schizophrenia - chemically induced; Schizophrenia - metabolism; Schizophrenia - physiopathology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.11.058

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+30mg/kg ketamine, 100mg/kg sarcosine+30mg/kg ketamine, and 15mg/kg clozapine+30mg/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.