Lower Sensitivity to Stress and Altered Monoaminergic Neuronal Function in Mice Lacking the NMDA Receptor ε4 Subunit

NMDA-stimulated⁴⁵Ca²⁺ uptake into forebrain synaptosomes of adult GluRε4 mutant mice. The forebrain synaptosomes were preincubated at 37°C for 10 min, in the presence or absence of 100 μm MK-801. The assay was initiated by adding prewarmed buffer containing 1 μCi/ml ⁴⁵CaCl₂for 5 min, in the presence of 100 μm NMDA, NMDA plus 10 μm glycine (Gly), or NMDA plus Gly plus 1 mm spermidine (SPD). Eachcolumn represents the mean ± SEM (n = 8 for −MK-801 group; n = 6 for +MK-801 group). *p < 0.05, **p < 0.01, and ***p < 0.001 versus wild-type (−MK-801).

Expression of NMDA receptor subunit proteins in various regions of the adult GluRε4 mutant mouse brain. The amount of each NMDA receptor subunit was determined by Western blot analysis using antibodies against GluRζ, GluRε1, or GluRε2. The synaptosomal protein samples were prepared from various regions of the adult GluRε4 mutant mouse brain. FC, Frontal cortex;HIP, hippocampus; STR, striatum;THA, thalamus. Each column represents the mean ± SEM (n = 4). *p < 0.05 versus wild-type (+/+).

Monoamine metabolism in various regions of the adult GluRε4 mutant mouse brain. The tissue contents of monoamines and their metabolites in various regions were measured by HPLC with an electrochemical detector. a, MHPG/NE; b, DOPAC/DA; c, HVA/DA; d, 5-HIAA/5-HT. Each column represents the mean ± SEM (n = 8). *p < 0.05 and **p < 0.01 versus wild-type (+/+).

Locomotor activity in a novel environment in adult GluRε4 mutant mice. Locomotor activity and the number of rearing events in a novel environment were measured every 5 min for 30 min. Each column represents the mean ± SEM (n = 10–11). An ANOVA with repeated measures revealed no difference in the time course of locomotion (F_(1,19) = 0.192; p= 0.9651) and rearing (F_(1,19) = 1.180;p = 0.3253). **p < 0.01 versus wild-type (+/+).