Fig. 7

Pharmacological amelioration of behavioral dysfunctions in Hbegf cKO mice. a, Time schedule of drug treatments and behavioral tests. b-d, Effects of compounds on hyperactivity and anxiety in the OF test. Results are shown as moving time: (b), moving distance: (c) and center time: (d) in the OF test. n = 23, 24, 18, 15, and 14, respectively, for Control-Saline, cKO-Saline, cKO-Atomoxetine, cKO-D-cycloserine, and cKO-Nefiracetam. e, Effects on impulsive behavior. Immobility times on the platform (s) were evaluated in the CA test. n = 23, 27, 19, 18, 16, respectively, for the groups mentioned above. f-h, Effects on dysfunction in contextual-: (f) and cue-exposed freezing: (g), and activity suppression ratio: (h) using the fear conditioning test. All data are shown as the percent of total freezing. n = 8, 9, 10, 16, 10, respectively, for the groups mentioned above. i and j, Effects on memory deficit using the step-through passive avoidance (PA) test. In the training session, each chronic drug administration did not change the PA latency: (i). Atomoxetine further decreased the PA latency in Hbegf cKO mice, while the decrease induced by D-cycloserine and nefiracetam was slight, but not significant: (j). The numbers of animals used were 10, 14, 10, 16, and 18, respectively. k and l, Effects on the obsessive behavior in Hbegf cKO mice. Both D-cycloserine and nefiracetam, but not atomoxetine reversed obsessive behavior in the MB test. Representative pictures of the results of the MB test 30 min after the start of the experiment: (k). Quantitative comparison of the numbers of buried marbles: (l). The numbers of animals used were 12, 18, 18, 15, and 16, respectively. m-o, Effects on decreased social activity. Typical pictures of differential pharmacological effects on nest building behavior: (m). Quantitative comparison on the rating scale: (n) and the levels of unused Nestlets: (o). The numbers of animals used were 8, 9, 8, 16, and 6, respectively. Values are the means ± s.e.m