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. 2018 Aug 14;43(11):2299–2309. doi: 10.1038/s41386-018-0178-6

Fig. 4.

Fig. 4

BPN14770 improves cognitive performance in wild-type and humanized PDE4D mice in Y-maze and NOR without causing significant reduction in ketamine/xylazine-induced anesthesia at cognitive-beneficial doses. a BPN14770 treatment increased % alternation in Y-maze in both wild-type and hPDE4D mice (n = 10 male mice); #p < 0.05 and *p < 0.05 versus vehicle-treated hPDE4D and wild-type mice, respectively (Dunnett’s multiple comparison test); H-89, a PKA inhibitor, was administered i.c.v. prior to dosing with BPN14770, $$p < 0.001 (Student’s t-test) versus hPDE4D mice treated with 0.03 mg/kg BPN14770. b Rolipram treatment increased % alternation in Y-maze in both wild-type and hPDE4D mice (n = 10 male mice); #p < 0.05 and *p < 0.05 versus the vehicle -treated hPDE4D and wild-type mice, respectively (Dunnett’s multiple comparison test). c BPN14770 treatment increased discrimination index in NOR in both wild-type and hPDE4D mice (24 h inter-trial interval, n = pooled analysis of 9–18 males and 5–9 females per group); #p < 0.05 or **p < 0.01 versus vehicle-treated group (Dunnett’s multiple comparison test); $p < 0.05 (Student’s t-test) versus humanized PDE4D mice treated with 0.03 mg/kg BPN14770. d Rolipram treatment increased discrimination index in NOR in both wild-type and hPDE4D (24 h inter-trial interval, n = pooled analysis of 8–10 males and 6–10 females per group); *p < 0.05 or #p < 0.05 versus the vehicle group of the identical genotype (Dunnett’s multiple comparison test). e Single acute treatment with BPN14770 reversed the memory impairment induced by scopolamine in NOR (1 h inter-trial interval, n = 9–10 mice per group). f Repeated treatment with BPN14770 for 14 days reversed the memory impairment induced by scopolamine in NOR (inter-trial interval, n = 10 mice per group). Data are presented as mean ± SEM (n = 10 males); *p < 0.05 or **p < 0.01 (Student’s t-test) versus vehicle-treated mice; $p < 0.05 and $$p < 0.01 (Dunnett’s multiple comparison) versus scopolamine-treated mice. g A high dose of BPN14770 reduced the ketamine/xylazine-induced anesthesia duration in hPDE4D mice (n = pooled analysis of 4–5 males and 4–5 females per group); **p < 0.01 (Student’s t-test) versus vehicle-treated wild-type group; #p < 0.05 or ##p< 0.01 (Student’s t-test) versus vehicle-treated hPDE4D group