Fig. 4.

Attenuated female response to ketamine during the follicular phase. a Representative vaginal smears during Estrus, Metestrus, Diestrus, and Proestrus stages of the estrous cycle. b Ketamine-induced changes of maximal evoked response in C57Bl/6J females during the follicular phase (Estrus/Proestrus, red filled circles, n = 87 cells; 5 mice) and luteal phase (Metestrus/Diestrus, gray circles, n = 82 cells; 6 mice) (median ± 95% CI; asterisk refers to Friedman test with Dunn’s multiple comparison vs baseline; hash refers to Kruskal–Wallis with Dunn’s multiple comparison follicular vs luteal). Dotted line, C57Bl/6J male values for comparison (n = 67 cells/4 mice). c Representative in situ hybridization images of female mouse V1 showing different categories of Pvalb-positive cells. d Integrated density of Pvalb mRNA in luteal and follicular stages (median ± 95% CI, n = 81 and 90 cells; Kruskal–Wallis test, not significant). e Integrated density (IntDen) of grin2A mRNA in luteal and follicular stages (Mann–Whitney, p = 0.0016). Dotted line, median value in males. f Proportion of Pvalb-positive cells without grin2A (0), low level (L: IntDen < 15% percentiles in males), medium (M) or high level of grin2A expression (H: IntDen > 85% percentiles in males). Males (black) and females during luteal (gray) and follicular (red) phases (asterisk refers to χ²-test). g Positive correlation between Pvalb and grin2A expression in females