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Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.
- Source :
-
Behavioural brain research [Behav Brain Res] 2017 Jun 15; Vol. 328, pp. 62-69. Date of Electronic Publication: 2017 Apr 06. - Publication Year :
- 2017
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Abstract
- Background: Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats.<br />Methods: Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed.<br />Results: Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls.<br />Conclusions: Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Amphetamine pharmacology
Animals
Central Nervous System Stimulants pharmacology
Cognition drug effects
Cognition physiology
Dose-Response Relationship, Drug
Executive Function physiology
Female
Learning drug effects
Learning physiology
Male
Memory drug effects
Memory physiology
Motor Activity physiology
Pregnancy
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate metabolism
Recognition, Psychology physiology
Schizophrenic Psychology
Dizocilpine Maleate toxicity
Excitatory Amino Acid Antagonists toxicity
Executive Function drug effects
Motor Activity drug effects
Prenatal Exposure Delayed Effects
Recognition, Psychology drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7549
- Volume :
- 328
- Database :
- MEDLINE
- Journal :
- Behavioural brain research
- Publication Type :
- Academic Journal
- Accession number :
- 28390877
- Full Text :
- https://doi.org/10.1016/j.bbr.2017.04.004