Figure 1.
Dose-dependent effects of pregnenolone, haloperidol and clozapine on activities of WT and DAT KO mice in the open field.
(A–C) Cumulative distance traveled (A), cumulative vertical activity (B), and cumulative stereotypical activities (C) were monitored over a 2 h period following injection of vehicle, or 30 or 60 mg/kg Preg. N = 10–15 mice/genotype/treatment condition; ap<0.05, WT-Veh versus KO-Veh; bp<0.05, WT-Preg30 versus KO-Preg30; cp<0.05, within groups versus Veh; dp<0.05, within groups Preg30 versus Preg60.
Figure 2.
Effects of pregnenolone, haloperidol and clozapine on activities of WT and DAT KO mice in the open field.
Baseline activities were monitored over 30 min, the mice were injected (i.p.) with vehicle, or 30 or 60 mg/kg pregnenolone (Preg) and returned immediately to the open field for 2 h. Cumulative distance traveled (A), vertical activity (B), and stereotypical activities (B) are shown. (D–F) Cumulative post-injection activities after WT and DAT KO mice were administered (i.p.) vehicle, 0.2 mg/kg haloperidol (HAL), 2.0 mg/kg clozapine (CLZ), or 60 mg/kg Preg, and monitored for locomotor (D), rearing (E), and stereotypical (F) activities. N = 9–15 mice/genotype/treatment condition, ap<0.05, WT-Veh versus KO-Veh; bp<0.05, within groups versus Veh; cp<0.05, within groups HAL or CLZ versus Preg60.
Figure 3.
Pregnenolone rescues PPI in DAT KO mice.
WT and DAT KO mice were injected (i.p.) with vehicle, or 30, or 60 mg/kg Preg and were tested in PPI 5 min later. (A) Amplitude of the startle responses of WT and DAT KO mice. (B) PPI levels of WT and DAT KO mice. White bars represent WT and grey bars represent DAT KO performance. N = 9–14 mice/genotype/treatment condition; ap<0.05, WT-Veh versus KO-Veh; bp<0.05, WT-Preg30 versus KO-Preg30; cp<0.05, within groups versus Veh; dp<0.05, within groups Preg30 versus Preg60.
Figure 4.
Pregnenolone normalizes the episodic memory deficits in DAT KO mice.
WT and DAT KO mice were injected (s.c.) with vehicle or 60 mg/kg Preg for 14 consecutive days and were tested in the novel object recognition (A) and social transmission of food preference (B) tests for short-term (STM), long-term (LTM), and remote memory. Number of contacts with the novel and familiar objects in the novel object recognition test (C) and the amount of food consumed in the social transmission of food preference test (D) were analysed. For the novel object recognition test, N = 9–12, and for the social transmission of food preference test, N = 9–11.