Fig. 1
From: Clozapine generates obsessive compulsive disorder-like behavior in mice
Clozapine-treated mice showed over grooming behavior. a Schematic diagram of experimental procedure. Wild-type and Sapap3+/− adult mice were administered with either clozapine or placebo for 28 wks, starting from age of 12 wk. b Clozapine-treated wild-type mice showed increased repetitive grooming behavior. Mice were injected with clozapine or placebo pellets at the age of 12 wk. with 60-day interval pellet injection. Mice behavior was recorded for 2 h and analyzed at the age of 15, 20, 30, and 40 wk. (Two-way RM ANOVA, main effect of treatment; F(1,16) = 9.161, p = 0.008, main effect of time; F(3,48) = 5.525, p = 0.002, treatment x time interaction; F(3,48) = 2.981, p = 0.04, ** p < 0.01) (left). Grooming lasted more than 3 s was counted as a bout (Two-way RM ANOVA, main effect of treatment; F(1,16) = 6.073, p = 0.025, main effect of time; F(3,48) = 3.491, p = 0.023, treatment x time interaction; F(3,48) = 2.674, p = 0.058, * p < 0.05) (right). c Clozapine-treated Sapap3+/− mice showed increased repetitive grooming behavior earlier than clozapine-treated wild-type mice. Sapap3+/− mice were injected with clozapine or placebo pellets at the age of 12 wk. with 60-day interval pellet injection. Mice behavior was recorded for 2 h and analyzed at the age of 12, 15, 20, 30 and 40 wk. (Two-way RM ANOVA, main effect of treatment; F(1,12) = 16.99, p = 0.01, main effect of time; F(3,36) = 10.12, p < 0.001, treatment x time interaction; F(3,36) = 3.348, p = 0.03, * p < 0.05, ** p < 0.01) (left). Numbers of grooming bouts were counted from 2 h video-recording of grooming behavior. Grooming bouts were increased in Sapap3+/− mice after 18 wk. of clozapine treatment (Two-way RM ANOVA, main effect of treatment; F(1,12) = 14.16, p = 0.003, main effect of time; F(3,36) = 11.17, p < 0.001, treatment x time interaction; F(3,36) = 4.095, p = 0.013, ** p < 0.01) (right). d Fluoxetine treatment ameliorated overgrooming behavior in clozapine-treated wild-type mice (Two-way ANOVA, main effect of fluoxetine treatment; F(1,6) = 21.75, p = 0.003, main effect of clozapine treatment; F(1,6) = 9.27, p = 0.023, fluoxetine treatment x clozapine treatment interaction; F(1,6) = 7.071, p = 0.038, * p < 0.05, *** p < 0.001) n = 4 per group. All data are presented as means ± SEM