Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia

Neuroscience
K WedzonyW Zajaczkowski

Abstract

The malfunction of glutamatergic neurotransmission in the neonatal or postnatal periods may be a risk factor for the appearance of neuroanatomical, neurochemical or functional changes that are characteristic of schizophrenia. Thus, the present study was undertaken to investigate whether blockade of N-methyl-d-aspartate (NMDA) receptors in the postnatal period influences rat behavior in tests characterizing schizophrenia-like deficits such as psychomotor agitation, impairments of sensorimotor gating, working memory, and intensity of social interactions. (E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116), a competitive antagonist of NMDA receptors, was given postnatally (1.25 mg/kg on days 1, 3, 6, 9; 2.5 mg/kg on days 12, 15, 18; and finally 5 mg/kg on day 21, all injections s.c.), and rats were tested at 60 days old. We found that blockade of NMDA receptors in the postnatal period led to an enhancement of exploration, mimicking psychomotor agitation, impairments in sensorimotor gating as measured by a prepulse-evoked inhibition of acoustic startle response, and an impaired working memory, as measured by an increase in the latency to achieve accurate rate of response in the delayed alternation task. Decreases in non-a...Continue Reading

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Apr 17, 2009·Psychopharmacology·Takashi UeharaMasayoshi Kurachi
Jul 1, 2009·Genes, Brain, and Behavior·T B HaleneS J Siegel
Aug 3, 2012·Expert Review of Neurotherapeutics·Emerson A NunesSerdar M Dursun
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Jan 18, 2011·Pharmacology, Biochemistry, and Behavior·A Basta-KaimK Wędzony
Dec 3, 2016·Pharmacological Reports : PR·Joachim LatuszMarzena Maćkowiak

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