N-Methyl-D-aspartate (NMDA)-type glutamic acid receptors play a critical role in excitatory synaptic transmission, synaptic plasticity and neuronal development in the central nervous system. During the developmental stage from week 25 of gestation to birth in humans, elongation and branching of axons and dendrites of nerve cells, synapse formation, myelination and realignment of nerve pathways (neural circuits) for acquiring higher neural function actively proceed, and this stage corresponds to postnatal weeks 1 through 2 in mice.1) It is generally recognized that non-synapse-mediated intercellular glutamic acid is largely involved in this process of nerve development. Stimulation of NMDA receptors facilitated radial migration of the cortical plate of excitatory nerve cells 2) and the selective blockade of NMDA receptors disturbed neuronal migration in the cerebral cortex.3)It has been reported that rats injected subcutaneously (s.c.) with phencyclidine (PCP), a noncompetitive NMDA receptor antagonist, at 10 mg/kg once a day during the postnatal development stage (postnatal days 7, 9 and 11) exhibit an increase in spontaneous motor activity, impairment of prepulse inhibition and behavioral changes in respect of learning and cognition after attaining maturation.4-7) When rats neonatally administered PCP were examined for any changes in the binding capacity of NMDA receptors and g-aminobutyrate A (GABA A ) receptors at maturity by autoradiography using In the present study, we investigated brain function from the behavioral, anatomical and neurochemical viewpoints in mice injected with PCP at 10 mg/kg on postnatal days 7, 9 and 11. Especially, we focused on changes in social interaction in PCP-treated mice, and examined the effects of clozapine, an atypical antipsychotic drug, D-cycloserine, an NMDA receptor partial agonist, flumazenil, a benzodiazepine receptor antagonist, and SHC50911, a GABA B receptor antagonist on social interaction deficits in PCP-treated mice. Of note, as far as we are aware, this is the first experimental demonstration that neonatal PCP treatment in mice results in increased sensitivity to PCP, and impaired social interaction behaviors in adulthood, which are accompanied by a decrease in the number of GABAergic interneurons and spine density in the frontal cortex and hippocampus, and abnormal monoamine metabolism in the brain. Neonatal PCP treatment in mice could be regarded as a neurodevelopmental animal model for schizophrenia. MATERIALS AND METHODSMethods. Animals Male mice aged 13 weeks old and female mice aged 13 weeks old Crlj:CD1 (ICR) were mated, and male offspring were used on postnatal day 7. Animals were maintained in a room controlled at 23°C and 55% humidity with a 12-h lighting cycle (lights on: 6:00 a.m.), and 12 ventilations/h. Animals had free access to solid feed (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan) from feed- Kakuma-machi, Kanazawa 920-1192, Japan: b Nihon Bioresearch Inc.; 6-104 Majima, Fukuju-cho, Hashima, Gifu 501-6251, Japan: c Narabyouri Research Co.,...

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We demonstrated that chronic treatment with milnacipran or fluvoxamine was effective to improve both the hyperemotional behavior and the loss of TPH-positive cells seen in OBX rats.

Histopathological study of the endstage kidney in a 50‐year‐old male who died after intermittent maintainance hemodialysis for 10 years was reported. At autopsy, both kidneys were contracted and characterized by grossly visible discrete multiple cysts. Histopathological study of consecutive sections of both kidneys revealed that these cysts were distributed throughout a completely disorganized parenchyma and were composed of dysplastic epithelial cells of different types and of structures, some of which revealed neoplastic transformation.

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