Modulatory effects of an NMDAR partial agonist in MK-801-induced memory impairment. (17th December 2015)

• Record Type: Journal Article
• Authors: Vishnoi, S.; Raisuddin, S.; Parvez, S.
• Is Part Of: Neuroscience. Volume 311(2015)
• Page Start: 22
• Page End: 33
• Publication Date: 2015-12-17
• Subjects: ACh acetyl choline -- AChE acetylcholinesterase -- ANOVA analysis of variance -- ATC acetyl thio choline iodide -- BAHC benzyl amine hydrochloride -- BDNF brain-derived neurotrophic factor -- BSA bovine serum albumin -- CTA conditioned taste aversion -- DAB diaminobenzidine -- DCS d-cycloserine -- DTNB 5, 50-dithiobis (2-nitrobenzoic acid) -- LTP long-term potentiation -- MAO mono amine oxidase -- NMDA N-methyl-d-aspartate -- NMDAR N-methyl-d-aspartate receptor -- NOR novel object recognition -- OF open field -- PCA perchloric acid -- PFC prefrontal cortex; NMDAR -- Behavior -- MK-801 -- d-cycloserine -- Dopamine -- c-fos; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.10.008
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Neurobehavioral deficits induced by MK-801 were inhibited by DCS. DCS counteracted MK-801 induced increase in dopamine level, AChE & MAO activity. DCS controlled the degree of overexpression of c-fos induced by MK-801. Improving NMDAR function by DCS may play vital role in neuropsychiatric disorders. Abstract: Rationale: Acute administration of the N-methyl-d -aspartate (NMDA) non-competitive antagonist, MK-801, impairs novel object recognition (NOR), locomotor activity in open field (OF) and conditioned taste aversion (CTA) in rodents. NMDAR partial agonistd -cycloserine (DCS) reverses these effects in NOR and CTA via modulation of glutamatergic, cholinergic and dopaminergic systems. Objectives and methods: To test this hypothesis, we investigated the effects of DCS, a partial NMDAR agonist, on NOR memory, locomotor activity, and CTA memory in Wistar rats on NMDA-glutamate receptor antagonism by MK-801. The potential involvement of dopaminergic and cholinergic systems in improving cognitive functions was explored. MK-801-induced cognitive deficits were assessed using NOR, OF and CTA paradigms. MK-801-induced dopamine release increase in acetylcholinesterase (AChE), mono amine oxidase (MAO) activity and increase in c-fos expression were also investigated. Results: The effects caused by MK-801 (0.2 mg/kg) were inhibited by administration of the NMDA receptor agonist DCS (15 mg/kg). NOR and CTA paradigms inhibited by MK-801 were attenuated by DCS administration. Moreover, DCS also blocked the MK-801-induced abnormal increase in dopamine content, AChE activity and MAO activity. However, c-fos overexpression was controlled to some extent only. Conclusions: Based on the NMDAR hypo function hypothesis in some neuropsychiatric disorders, our finding suggests that improving NMDAR hypo function by agonist DCS may play a significant role.