Fig. 3. Sexual dichotomy in anxiety-like behaviors of double-mutant mice. Decreased anxiety-like behavior of double-mutant animals as measured in the elevated plus maze (A, B) test of anxiety is shown. All tests were conducted on individually housed 16- to 20-week-old female and male mice. All results are reported as mean ± SEM. A, Percentage of time spent in the open arms and number of entries into the open arms were significantly more for the female double-mutant mice (n = 27) than for the wild-type controls (n = 27) (*p < 0.05). Female CRFR1-mutant mice were not significantly different from controls (n = 4). B, Percentage of time spent in the open arms and number of entries into the open arms were not significantly different between male double-mutant mice (n = 11), CRFR1-mutant mice (n= 8), and wild-type mice (n = 10).C, Comparison of males and females on the open-field test. Male double-mutant mice spend significantly less time in the center of the open field than double-mutant females (n = 10 males; n = 16 females; *p < 0.05). No significant differences were found between male and female wild-type mice (n = 10 males; n = 24 females; p = 0.63) or CRFR1-mutant mice (n = 8 males;n = 5 for females; p = 0.06).D, A significant correlation was found between the dam's CRFR2 genotype and the male pup's anxiety-like behavior. If the mother was heterozygous or homozygous for CRFR2 mutation, the pup, regardless of its genotype, showed significantly more anxiety-like behavior (as measured by time spent on the open arm of the elevated plus maze). **Significantly different (p < 0.05). For male pups born to wild-type dams, n = 4 CRFR1-mutant mice and n = 6 wild-type mice. For male pups born to either heterozygous or mutant dams,n = 4 CRFR1-mutant mice, n = 11 double-mutant mice, and n = 4 wild-type mice. For female pups born to wild-type dams, n = 3 CRFR1-mutant mice and n = 18 wild-type mice. For female pups born to either heterozygous or mutant dams,n = 2 CRFR1-mutant mice, n = 27 double-mutant mice, and n = 9 wild-type mice.