Figure 6. Hippocampal hypermetabolism and volume loss induced by repeated ketamine administration is ameliorated by a glutamate release inhibitor.

(A) rCBV following repeated treatment over one month with ketamine and co-treatment with either saline (red bars) or LY379268 10mg/kg (blue bars). Co-treatment with LY379268 ameliorated the repeated ketamine-induced increase in basal hippocampal rCBV, as evident from comparison with saline pretreatment. The saline/ketamine group is the same as that previously shown in Figure 4. * p < 0.05 relative to saline.

(B) LY379268 (10mg/kg) co-treatment during repeated ketamine exposure (blue bars) ameliorated the hippocampal (HIPP) volume loss, as evidenced by significantly preserved (larger) HIPP volume in the LY 379268 (blue symbols) relative to the saline co-treatment group (red symbols). ** p < 0.01 relative to saline/ketamine.

(C) Rostral view of morphometric shape change map. Pre-treatment with LY379268 resulted in protection in the CA fields of the hippocampal body as measured by MRI-based morphometric analysis; areas of statistically significant volume protection are shown by orange clusters.

(D) Average cross-sectional hippocampal area (mm²) in fixed brains of mice represented in Panels A–C. Volume protection of LY379268 pre-treatment is most evident in the caudoventral aspect of the hippocampus (see main text for anatomical boundaries).

*p < 0.05 relative to saline co-treatment ; for all groups, the saline/ketamine group is the same as that represented in Figure 5.

Data for panels A, B, and D are represented as mean ± SEM.