Impact of postnatal blockade of N-methyl-d-aspartate receptors on rat behavior: A search for a new developmental model of schizophrenia
| Autor: | Wojciech M. Zajaczkowski, Katarzyna Fijał, Agnieszka Chocyk, Marzena Maćkowiak, Krzysztof Wędzony |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Reflex Startle medicine.medical_specialty Psychosis Elevated plus maze Startle response Phencyclidine Receptors N-Methyl-D-Aspartate Pregnancy Internal medicine medicine Animals Rats Wistar Maze Learning Social Behavior 2-Amino-5-phosphonovalerate Analysis of Variance Behavior Animal Dose-Response Relationship Drug medicine.diagnostic_test General Neuroscience Age Factors medicine.disease Startle reaction Rats Disease Models Animal Endocrinology Animals Newborn Schizophrenia Exploratory Behavior NMDA receptor Female Psychology Excitatory Amino Acid Antagonists Neuroscience Psychomotor Performance medicine.drug |
| Zdroj: | Neuroscience. 153:1370-1379 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2008.03.016 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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