Responses to neurosteroids in PKCε-null mice. (a) Muscimol-stimulated 36Cl uptake in the presence of 1 nM allopregnanolone (n = 11 of each genotype) or 1 μM pregnanolone (n = 4 of each genotype) was greater in tissue from hybrid PKCε-null compared with tissue from hybrid wild-type mice (two-tailed t tests). (b) Microsacs from frontal cortex of hybrid PKCε-null mice (open circles) show greater muscimol-stimulated 36Cl uptake in the presence of alphaxalone compared with microsacs from hybrid wild-type mice (filled circles). Nonlinear regression analysis revealed an increased maximal response to alphaxalone in PKCε-null mice (409.4 ± 26.5%; n = 4–8) compared with wild-type mice (247.1 ± 26.9%, P = 0.005; n = 4–6), without a difference in log ED₅₀ values (–6.86 ± 0.14 in PKCε-null and –6.62 ± 0.20 in wild-type mice; P = 0.826). (c) The duration of the pregnanolone-induced loss of the righting reflex (LORR) was greater (P = 0.008; two-tailed unpaired t test) in hybrid male PKCε-null mice (n = 9) compared with wild-type male littermates (n = 8). (d) Total brain levels of alphaxalone were similar in hybrid wild-type (n = 8) and PKCε-null (n = 9) mice.