Neonatal exposure to the glutamate receptor antagonist MK-801: effects on locomotor activity and pre-pulse inhibition before and after sexual maturity in rats

Neurotoxicity Research
R. J. BeningerK. Jhamandas

Abstract

Neonatal lesions of the ventral hippocampus in rats lead to post- but not pre-pubertal behavioral changes suggesting adolescent onset of dopaminergic hypersensitivity and providing an animal model of schizophrenia. Neonatal exposure to glutamate receptor antagonists produces accelerated apoptosis leading to neuronal loss in central nervous system structures including the hippocampus. This suggested that neonatal MK-801 might lead to behavioural changes like those reported following ventral hippocampal lesions. Thus, rats received MK-801 (0, 0.5, 1.0 mg/kg ip) on postnatal day 3 (P3) and were tested pre- (P35) and post-pubertally (P56). MK-801 produced an increase in TUNEL staining in the hippocampus and other forebrain structures, confirming the induction of apoptosis. Results showed little difference in locomotor activity between neonatal saline- and MK-801-treated groups during habituation or following saline injection but increased activity was seen in the 0.5 mg/kg MK-801 group following amphetamine (1.5 mg/kg i.p.) at P35 but not P56. In tests of pre-pulse inhibition (PPI), neonatal saline and MK-801 groups showed stable startle amplitudes, minimal responding to the pre-pulse stimuli alone, an increase in PPI with increase...Continue Reading

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Citations

Jan 13, 2004·Neurotoxicity Research·Richard M Kostrzewa, Juan Segura-Aguilar
Apr 17, 2009·Psychopharmacology·Takashi UeharaMasayoshi Kurachi
May 20, 2003·Neurotoxicity Research·Tomás PalomoRichard J. Beninger
Jul 1, 2010·Expert Review of Neurotherapeutics·Trevor Archer
Jan 20, 2009·Brain Research Bulletin·Jozsef FarkasPeter Kiss
Nov 23, 2017·Frontiers in Molecular Neuroscience·Alessandra PaparelliNori Takei
Jul 1, 2017·Frontiers in Cellular Neuroscience·Marta Perez-RandoJuan Nacher
Nov 19, 2004·The European Journal of Neuroscience·John G HowlandAnthony G Phillips
May 4, 2021·Neural Plasticity·Xiaodan WangDonghong Cui

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