title: Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats.
abstract: The present study was carried out to evaluate whether the combined administration of sarcosine with risperidone possess any advantageous effects on dopaminergic and NMDA receptor-mediated glutamatergic neurotransmissions as compared to single drug administration in rats. The Wistar rats were divided into 7 groups each with different treatments. MK-801 (0.1 mg/kg, i.p.) was injected as single dose on 14th day for inducing learning and memory deficits in animals. Sarcosine (300 and 600 mg/kg, i.p.) and risperidone (0.2 mg/kg, i.p.) were administered daily for 14 days. Spatial habituation learning and hole board tests were performed on 14th day followed by measurement of GABA and 5-HT levels in brain tissues of rats. Pretreatment of sarcosine (600 mg/kg, i.p.) non-significantly improved learning and memory deficits induced by non-competitive NMDA receptor antagonist MK-801, significantly increased the GABA and decreased the 5-HT levels (p<0.05). Combined administration of sarcosine (300 mg/kg, i.p.) with risperidone (0.1 mg/kg, i.p.) synergistically improved cognitive deficits significantly, decreased % errors in hole board learning test, and increased centre time, corner time in spatial habituation learning test (p<0.05). The combined administration also potentiated the GABA and decreased 5-HT levels, indicating that the increased synaptic glycine concentrations may enhance NMDA receptor function which is directly linked with increased GABAergic transmission in striatum region and decreased 5-HT levels showed antagonistic action hence, enhancing the cognition. Our results suggest that combined administration of sarcosine with risperidone may strengthen glutamatergic tone in striatum. Thus, it may be a novel regime to improve psychotic symptoms and cognitive deficit in schizophrenia.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: M A
authors.initials: MA
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Najmi
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Akhtar
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology*; D012521:Sarcosine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D050487:Glycine Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D018967:Risperidone; D005998:Glycine; D012521:Sarcosine