Figure 4. Chronic administration of olanzapine, but not clozapine, triggers the increase of extracellular D-aspartate and L-glutamate in the prefrontal cortex of mice.

(a) Schematic timeline of the chronic antipsychotic drugs administration procedure and microdialysis. (b,c) Time course of free (b) D-Asp and (c) L-Asp extracellular concentration in the prefrontal cortex (PFC) of mice chronically treated with 5 mg/kg olanzapine and their relative vehicle-treated controls (n = 8 vehicle, n = 5 olanzapine). (d) Free D-Asp and (e) L-Asp total content in PFC homogenates of chronically olanzapine-treated mice and their relative vehicle-treated controls (n = 5 vehicle, n = 7 olanzapine). (f,g) Time course of free (f) D-Asp and (g) L-Asp extracellular concentration in the PFC of mice chronically treated with 5 mg/kg clozapine and their relative vehicle-treated controls (n = 5 per treatment). (h) Free D-Asp and (i) L-Asp total content in PFC homogenates of chronically clozapine-treated mice and their relative vehicle-treated controls (n = 10 per treatment). The amount of free D-Asp and L-Asp in tissue homogenates was normalized by the total protein content of each sample. (j,k) Time course of free L-Glu extracellular concentration in mice subjected to the chronic administration of 5 mg/kg (j) olanzapine or (k) clozapine and their relative vehicle-treated controls. We used the same cohorts of animals to concomitantly detect D-Asp, L-Asp and L-Glu. The graphs display the mean values ± SEM. **P < 0.01, compared to vehicle-treated mice (Student’s t test).