(A) Schematic of pharmacotherapy with Lutrelef, a clinically-used GnRH peptide, in adult Ts65Dn mice. Mice were implanted with osmotic pumps to receive a continuous infusion of vehicle or Lutrelef (0.25 μg/3h over 2 weeks), or with a programmable mini-pump (iPRECIO), to receive pulsatile Lutrelef infusion (0.25 μg/10 min every 3 hours over 2 weeks). (B-I) Effect of treatments on odor discrimination (B; n=4,8,3,5,6 mice), object recognition (C; n=4,9,4,4,8 mice) and LH pulsatility (D-I) (D: n=4,9,3,4,8 mice; each dot represents one subject). (J-K) Effects of Lutrelef in orchidectomized (ORX) mice (n=4). Values represent means ± SEM. * P<0.05,** P<0. 01,***P<0.001; paired Student’s t-test or Wilcoxon matched-pair test (B,C), unpaired Student’s t-test or Mann-Whitney U-test (D) or a two-way repeated-measures ANOVA followed by Sidak’s post hoc test (J,K).