P.1.h.041 Effect of fluoxetine and alprazolam on escape response induced by hypoxia

Abstract

effects on behavior, gene expression and DNA methylation in the hippocampus, particularly of female 5-Htt+/− offspring. To follow up this interaction, in the present study we aim to investigate the role of a PS x 5-Htt interaction in resilience in female wild type (5-Htt+/+) and heterozygous (±) 5-HTT deficient offspring. To this end, we applied the maternal restraint stress paradigm of PS in female 5-Htt+/+ and 5-Htt+/− mice from E13 to E17, three times a day. We then analyzed behavioral parameters related to anxietyand depressive-like behavior as well as hypothalamic– pituitary–adrenal axis function in the adult female offspring. We found that the PS mice spent less time with a conspecific animal in the 3-chamber-sociability test than controls (p = 0.012, 2-factorial ANOVA). Based on the sociability data, we separated 5-Htt+/+ and 5-Htt+/− PS offspring into a ‘normally social’, resilient group, comparable to control animals, and an ‘unsocial’, susceptible group, which showed no preference for spending time with the conspecific animal, in contrast to the control group. Locomotor activity, basal and stress-induced corticosterone levels, anxietylike behavior in the EPM, behavioral despair in the Porsolt swim test and anhedonia in the sucrose preference were analyzed based on the classification in resilient and susceptible groups. While susceptible PS 5-Htt+/+ animals showed less anxiety-like behavior in the elevated plus maze when compared to control 5-Htt+/+ mice (Man-Whitney-U Bonferroni-Holmes corrected p = 0.032), this effect was not found for the 5-Htt+/− genotype animals. On the other hand, susceptible 5-Htt+/− mice showed a trend for increased basal corticosterone levels (Man-Whitney-U BonferroniHolmes corrected p = 0.071), whereas no differences for basal corticosterone were found for 5-Htt+/+ animals. No effects of PS or genotype were observed in the Porsolt swim test and the sucrose preference test. Thus, our findings indicate a modulating role of the 5-Htt genotype on the role of resilience towards PS in female mice. Next on our agenda, we aim to identify the molecular players that are mediating the interaction between PS and the 5-Htt genotype in the context of vulnerability and resilience to PS. For this purpose, gene expression profiles of the hippocampus are currently being analyzed using mRNAseq. Arising candidate genes will then be validated using qPCR and analyzed in regard of DNA methylation and histone modifications.