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Drug Res (Stuttg) 2016; 66(01): 11-17
DOI: 10.1055/s-0035-1545299
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Sarcosine (a Glycine Transport 1 Inhibitor) and Risperidone (an Atypical antipsychotic Drug) on MK-801 Induced Learning and Memory Deficits in Rats

V. Kumar
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
M. A. Ahmad
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
A. K. Najmi
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
,
M. Akhtar
1   Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
› Author Affiliations
Further Information

Publication History

received 28 October 2014

accepted 27 January 2015

Publication Date:
24 February 2015 (online)

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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.

Key words

sarcosine - NMDA receptor - glyceine transport inhibitor - GABA - 5-HT
 

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