Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Nov 2010
Late prenatal immune activation in mice leads to behavioral and neurochemical abnormalities relevant to the negative symptoms of schizophrenia.
Based on the human epidemiological association between prenatal infection and higher risk of schizophrenia, a number of animal models have been established to explore the long-term brain and behavioral consequences of prenatal immune challenge. Accumulating evidence suggests that the vulnerability to specific forms of schizophrenia-related abnormalities is critically influenced by the precise timing of the prenatal immunological insult. In the present study, we tested the hypothesis whether late prenatal immune challenge in mice may induce long-term behavioral and neurochemical dysfunctions primarily associated with the negative symptoms of schizophrenia. ⋯ In addition, male but not female offspring born to immune challenged mothers displayed behavioral/cognitive inflexibility as indexed by the presence of an abnormally enhanced latent inhibition (LI) effect. Prenatal immune activation in late gestation also led to numerous, partly sex-specific changes in basal neurotransmitter levels, including reduced dopamine (DA) and glutamate contents in the prefrontal cortex and hippocampus, as well as reduced γ-aminobutyric acid (GABA) and glycine contents in the hippocampus and prefrontal cortex, respectively. The constellation of behavioral and neurochemical abnormalities emerging after late prenatal Poly-I:C exposure in mice leads us to conclude that this immune-based experimental model provides a powerful neurodevelopmental animal model especially for (but not limited to) the negative symptoms of schizophrenia.
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Neuropsychopharmacology · Nov 2010
Effects of the nitric oxide synthase inhibitor L-NAME on recognition and spatial memory deficits produced by different NMDA receptor antagonists in the rat.
There is consistent experimental evidence that noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor, such as ketamine, MK-801, and phencyclidine (PCP), impair cognition and produce psychotomimetic effects in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain. The implication of NO in learning and memory is well documented. ⋯ L-NAME (10 mg/kg) attenuated ketamine (15 mg/kg)-induced spatial working memory and retention deficits in the radial water maze paradigm. L-NAME, applied at 3 mg/kg, however, disrupted rodents' performance in this spatial memory task. The present findings indicate (1) that L-NAME is sensitive to glutamate hypofunction produced by other than PCP NMDA antagonists such as MK-801 and ketamine and (2) that L-NAME alone differentially affects rodents' spatial memory.