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Prophylactic ( R,S )‐ketamine Protects Against Fear Overgeneralization 8.5.5
Author(s) -
Diaz Cesar,
Mastrodonato Alessia,
Denny Christine
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03313
Subject(s) - dentate gyrus , hippocampal formation , context (archaeology) , hippocampus , anxiety , neurogenesis , psychology , neuroscience , nmda receptor , medicine , psychiatry , biology , receptor , paleontology
The adolescent stage is a sensitive time period for brain development. During this phase, the brain's high plasticity makes adolescents more susceptible to external factors, one of these being stress. Anxiety and mood disorders such as post‐traumatic stress disorder (PTSD) and major depressive disorder (MDD) mainly stem from exposure to stress. Studies have shown that a single injection of (R,S)‐ketamine, an NMDA antagonist, prior to stress protects against the development of depressive‐like behavior and attenuates learned fear. However, most of these studies were conducted in post‐natal day 60 (P60) adult mice. We sought to identify the neural correlates of fear in post‐natal day 35 (P35) adolescent mice and which neural alterations correlate to fear generalization. In the experiment, ArcCreERT2 P60 and P35 mice were administered a pattern separation (PS) paradigm. The mice were then sacrificed, and their brains were processed on either day 3 (D3) or day 10 (D10) following context A or B exposures, respectively. Through cell quantification and hippocampal analysis, we saw that during the PS task, both groups of mice exhibited comparable levels of freezing following one‐shock in the aversive context A. However, when compared to P60 mice, the P35 mice tend to over‐generalize fear. P35 mice distinguish between the two contexts on Day 8, whereas P60 mice distinguish between the two contexts starting on Day 6. This behavioral phenotype seems to be mainly mediated by CA3 but not the Dentate Gyrus in the hippocampus. Our data indicate that P35 adolescent mice over‐generalize fear when compared to P60 adult mice. It also reveals that the CA3 in the hippocampus is what mediates contextual discrimination in these adolescent mice. In the future, these results encourage us to introduce ketamine to P35 adolescent mice. This would allow us to explore the mechanisms involved in fear generalization between P35 and P60 mice and if ketamine would have the same effect on them. 8.5.5