Abstract:
BACKGROUND:We previously reported that a single injection of ketamine prior to stress protects against the onset of depressive-like behavior and attenuates learned fear. However, the molecular pathways and brain circuits underlying ketamine-induced stress resilience are still largely unknown. METHODS:Here, we tested whether prophylactic ketamine administration altered neural activity in the prefrontal cortex and/or hippocampus. Mice were injected with saline or ketamine (30 mg/kg) 1 week before social defeat. Following behavioral tests assessing depressive-like behavior, mice were sacrificed and brains were processed to quantify ΔFosB expression. In a second set of experiments, mice were stereotaxically injected with viral vectors into ventral CA3 (vCA3) in order to silence or overexpress ΔFosB prior to prophylactic ketamine administration. In a third set of experiments, ArcCreERT2 mice, a line that allows for the indelible labeling of neural ensembles activated by a single experience, were used to quantify memory traces representing a contextual fear conditioning experience following prophylactic ketamine administration. RESULTS:Prophylactic ketamine administration increased ΔFosB expression in the ventral dentate gyrus and vCA3 of social defeat mice but not of control mice. Transcriptional silencing of ΔFosB activity in vCA3 inhibited prophylactic ketamine efficacy, while overexpression of ΔFosB mimicked and occluded ketamine's prophylactic effects. In ArcCreERT2 mice, ketamine administration altered memory traces representing the contextual fear conditioning experience in vCA3 but not in the ventral dentate gyrus. CONCLUSIONS:Our data indicate that prophylactic ketamine may be protective against a stressor by altering neural activity, specifically the neural ensembles representing an individual stressor in vCA3.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Mastrodonato A,Martinez R,Pavlova IP,LaGamma CT,Brachman RA,Robison AJ,Denny CAdoi
10.1016/j.biopsych.2018.02.011subject
Has Abstractpub_date
2018-12-01 00:00:00pages
846-856issue
11eissn
0006-3223issn
1873-2402pii
S0006-3223(18)30112-4journal_volume
84pub_type
杂志文章abstract::The role of developmental theory and developmental psychopathology in understanding the development, maintenance, and course of social anxiety disorder (SAD) is explored in this article. Following a brief examination of the phenomenology of SAD in youth, we provide an overview of the tenets of developmental psychology...
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