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Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia.
Neuroscience. 2008 Jun 02; 153(4):1370-9.N

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-aggressive social interactions and increases in aggressive interactions were also observed. In addition to cognitive deficits typical of schizophrenia, rats treated postnatally with NMDA receptor antagonists also showed higher level of fear exhibited in the elevated plus maze. Thus, the blockade of NMDA receptors in the postnatal period may model deficits that are characteristic of schizophrenia.

Authors+Show Affiliations

Institute of Pharmacology Polish Academy of Sciences, Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Smetna 12 Street, Kraków, Poland. nfwedzon@cyf-kr.edu.plNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18434025

Citation

Wedzony, K, et al. "Impact of Postnatal Blockade of N-methyl-D-aspartate Receptors On Rat Behavior: a Search for a New Developmental Model of Schizophrenia." Neuroscience, vol. 153, no. 4, 2008, pp. 1370-9.
Wedzony K, Fijal K, Mackowiak M, et al. Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia. Neuroscience. 2008;153(4):1370-9.
Wedzony, K., Fijal, K., Mackowiak, M., Chocyk, A., & Zajaczkowski, W. (2008). Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia. Neuroscience, 153(4), 1370-9. https://doi.org/10.1016/j.neuroscience.2008.03.016
Wedzony K, et al. Impact of Postnatal Blockade of N-methyl-D-aspartate Receptors On Rat Behavior: a Search for a New Developmental Model of Schizophrenia. Neuroscience. 2008 Jun 2;153(4):1370-9. PubMed PMID: 18434025.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of postnatal blockade of N-methyl-D-aspartate receptors on rat behavior: a search for a new developmental model of schizophrenia. AU - Wedzony,K, AU - Fijal,K, AU - Mackowiak,M, AU - Chocyk,A, AU - Zajaczkowski,W, Y1 - 2008/03/20/ PY - 2008/01/02/received PY - 2008/02/11/revised PY - 2008/03/08/accepted PY - 2008/4/25/pubmed PY - 2008/10/9/medline PY - 2008/4/25/entrez SP - 1370 EP - 9 JF - Neuroscience JO - Neuroscience VL - 153 IS - 4 N2 - 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-aggressive social interactions and increases in aggressive interactions were also observed. In addition to cognitive deficits typical of schizophrenia, rats treated postnatally with NMDA receptor antagonists also showed higher level of fear exhibited in the elevated plus maze. Thus, the blockade of NMDA receptors in the postnatal period may model deficits that are characteristic of schizophrenia. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18434025/Impact_of_postnatal_blockade_of_N_methyl_D_aspartate_receptors_on_rat_behavior:_a_search_for_a_new_developmental_model_of_schizophrenia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(08)00388-6 DB - PRIME DP - Unbound Medicine ER -