Figure 4. Repeated ketamine administration recapitulates the psychosis-associated pattern of hippocampal hypermetabolism and atrophy.

(A) Repeated intermittent ketamine administration over one month (8mg/kg, 16mg/kg, 32mg/kg vs. saline) led to a metabolic state change in hippocampal rCBV: it dose-dependently led to increases in basal rCBV measured at 48 hours after washout of the drug. Statistically significant increases were observed for the 8 and 16 mg/kg repeated treatments. * p < 0.05, relative to saline treatment. Data are represented as mean ± SEM.

(B) Compared to saline control, negative hippocampal volume change was found in mice receiving higher doses of repeated ketamine administration, with the effect asymptoting at 16 mg/kg. ** p < 0.01; *** p < 0.01, relative to saline treatment.

(C) Rostral view of morphometric shape change map. Compared to saline control, areas of negative hippocampal volume change were localized in the 16mg/kg group to the left ventral aspects of hippocampal body by morphometric shape analysis; areas of statistically significant volume loss are shown by orange clusters.

(D) Average cross-sectional hippocampal area (mm²) as measured in fixed tissue from a subset of mice shown in Panels A–C. Relative to the saline group saline (dark bars), mice receiving repeated ketamine 16 mg/kg (light gray stippled bars) for one month showed areal reductions in the caudoventral aspect of the hippocampus (see main text for anatomical boundaries). * p < 0.05 relative to saline. Data are represented as mean ± SEM. See also Figure S1.