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Behavioral and biochemical sensitivity to low doses of ketamine: Influence of estrous cycle in C57BL/6 mice.

ABSTRACT: RATIONALE:Low-dose ketamine is a rapid-acting antidepressant, to which female rodents are more sensitive as compared to males. However, the mechanism mediating this sex difference in ketamine sensitivity remains elusive. OBJECTIVES:We sought to determine whether male and female mice differ in their behavioral sensitivity to low doses of ketamine, and uncover how ovarian hormones influence females' ketamine sensitivity. We also aimed to uncover some of the molecular mechanism(s) in mood-related brain regions that mediate sex differences in ketamine antidepressant effects. METHODS:Male and female mice (freely-cycling, diestrus 1 [D1], proestrus [Pro], or D1 treated with an estrogen receptor (ER) ?, ER?, or progesterone receptor (PR) agonist) received ketamine (0, 1.5, or 3 mg/kg, intraperitoneally) and were tested in the forced swim test (FST) 30 min later. Ketamine's influence over synaptic plasticity markers in the prefrontal cortex (PFC) and hippocampus (HPC) of males, D1, and Pro females was quantified by Western blot 1 h post-treatment. RESULTS:Males, freely cycling females, D1 and Pro females exhibited antidepressant-like responses to 3 mg/kg ketamine. Pro females were the only group where ketamine exhibited an antidepressant effect at 1.5 mg/kg. D1 females treated with an agonist for ER? or ER? exhibited an antidepressant-like response to 1.5 mg/kg ketamine. Ketamine (3 mg/kg) increased synaptic plasticity-related proteins in the PFC and HPC of males, D1, and Pro females. Yet, Pro females exhibited an increase in p-Akt and p-CaMKII? in response to 1.5 and 3 mg/kg ketamine. CONCLUSION:Our results indicate that females' enhanced sensitivity to ketamine during Pro is likely mediated through estradiol acting on ER? and ER?, leading to greater activation of synaptic plasticity-related kinases within the PFC and HPC.

SUBMITTER: Dossat AM

PROVIDER: S-EPMC5749639 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Behavioral and biochemical sensitivity to low doses of ketamine: Influence of estrous cycle in C57BL/6 mice.

Dossat Amanda M AM Wright Katherine N KN Strong Caroline E CE Kabbaj Mohamed M

Neuropharmacology 20171121

<h4>Rationale</h4>Low-dose ketamine is a rapid-acting antidepressant, to which female rodents are more sensitive as compared to males. However, the mechanism mediating this sex difference in ketamine sensitivity remains elusive.<h4>Objectives</h4>We sought to determine whether male and female mice differ in their behavioral sensitivity to low doses of ketamine, and uncover how ovarian hormones influence females' ketamine sensitivity. We also aimed to uncover some of the molecular mechanism(s) in ...[more]

PMID: 29175352

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Project description:The vaginal microbiota plays an important role in the health of dairy cattle, and it could be manipulated for the prevention and treatment of reproduction-related infections. The present study profiles and compares the vaginal microbiota of healthy dairy heifers during the estrous cycle focusing the results in follicular (estrus) and luteal (diestrus) phases using 16S rRNA sequencing of the V3-V4 hypervariable region. Twenty 13-16-months-old virgin dairy heifers from a single farm were included in this study. Vaginal swabs and blood samples were obtained during estrus (6-8 h before artificial insemination) and diestrus (14 days after insemination). Estrus was evaluated by an activity monitoring system and confirmed with plasma progesterone immunoassay. Results showed that the taxonomic composition of the vaginal microbiota was different during the follicular and luteal phases. At the phylum level, the most abundant bacterial phyla were Tenericutes, Firmicutes, and Bacteroidetes which comprised more than 75% of the vaginal microbiota composition. The next more abundant phyla, in order of decreasing abundance, were Proteobacteria, Actinobacteria, Fusobacteria, Epsilonbacteraeota, and Patescibacteria. Together with Tenericutes, Firmicutes, and Bacteroidetes represented more than 96% of the bacterial composition. Ureaplasma, Histophilus, f_Corynebacteriaceae, Porphyromonas, Mycoplasma, Ruminococcaceae UCG-005, were the most abundant genera or families. The results also showed that the vaginal microbiota of dairy heifers was non-lactobacillus dominant. The genus Lactobacillus was always found at a low relative abundance during the estrous cycle being more abundant in the follicular than in the luteal phase. Despite more research is needed to explore the potential use of native vaginal microbiota members as probiotics in dairy heifers, this study represents an important step forward. Understanding how the microbiota behaves in healthy heifers will help to identify vaginal dysbiosis related to disease.

Dataset Information

Behavioral and biochemical sensitivity to low doses of ketamine: Influence of estrous cycle in C57BL/6 mice.

Publications

Behavioral and biochemical sensitivity to low doses of ketamine: Influence of estrous cycle in C57BL/6 mice.

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