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. Author manuscript; available in PMC: 2017 Dec 8.
Published in final edited form as: J Neurosci. 2017 Nov 3;37(49):11967–11978. doi: 10.1523/JNEUROSCI.1668-17.2017

Figure 5. Reversal of anxiety- and depression-like phenotypes upon loss of Freud-1 in the absence of 5-HT1A autoreceptors.

Figure 5

Tissues from mice with conditional knockout of Freud-1 and 5-HT1A receptor in adult serotonin neurons (cF1/1A dKO) were compared to 5-HT1A conditional knockout (c1AKO) or wild-type littermates (WT/WT). A. Tamoxifen-induced recombination. Co-staining for YFP and TPH in the dorsal raphe. Recombination occurred exclusively in 5-HT cells; 92% of TPH-positive cells were YFP-positive (scale bar = 100 μm). B. Loss of 5-HT1A autoreceptors. Immunostaining for 5-HT1A and TPH showed significant loss of 5-HT1A immunostaining in TPH-positive cells of cF1/1A dKO mice. White arrows indicate the presence of 5-HT1A receptors in non-TPH positive cells in dorsal raphe (scale=100 μm). C. 5-HT1A autoradiography. 5-HT1A receptor autoradiography using 125I-MPPI of representative midbrain sections from WT/WT and cF1/1A dKO mice, including dorsal (DR) and median (MR) raphe (boxes) and hippocampal sections. DR and MR showed significant decreases in 5-HT1A autoreceptor binding: DR (unpaired two-tailed Student’s t-test, DF=4, t=11.24, ***p<0.001), MR (unpaired two-tailed Student’s t-test, DF=4, t=5.235, *p<0.01). D–H. Behavioral studies were done in either wild-type (WT) or conditional knockout (KO) for Freud-1 (F1) and/or 5-HT1A receptor (1A) in littermate mice. D. EPM. No change in anxiety-like behavior (open arm time) was observed. E. OF. No difference among groups was observed in time spent in the large centre. F. NSF. The latency to feed was not altered. G. FST. Immobility duration was reduced in F1/1AKO vs. WT and 1AKO mice (one-way ANOVA genotype X genotype interaction, F2,25=4.463, p=0.0067; post-hoc Tukey *p<0.05 vs. WT, #p<0.05 vs. 1AKO). H. TS. Immobility time was reduced in F1/1AKO compared to WT or 1AKO (one-way ANOVA genotype X genotype interaction, F2,29=6.998, p=0.0033; post-hoc Tukey *p<0.05 vs. WT, #p<0.05 vs. F1/1AKO). I. Beam break test. No difference in 30-min activity in novel arena was observed. Data points represent individual mice, with mean ± SEM: WT, n=10; F1WT/1AKO, n=11; F1/1AKO, n=11.