ArticleJournal of neuroscience research2021
Isoxazole-9 reduces enhanced fear responses and retrieval in ethanol-dependent male rats.
Article in Journal of neuroscience research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
3 citing papers in PubMed.
- Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior.Behavioural brain research · 2025Article
- Abstinence and Fear Experienced during This Period Produce Distinct Cortical and Hippocampal Adaptations in Alcohol-Dependent Rats.Brain sciences · 2024Article
- ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude.Communications biology · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Plasticity in the dentate gyrus (DG) is strongly influenced by ethanol, and ethanol experience alters long-term memory consolidation dependent on the DG. However, it is unclear if DG plasticity plays a role in dysregulation of long-term memory consolidation during abstinence from chronic ethanol experience. Outbred male Wistar rats experienced 7 weeks of chronic intermittent ethanol vapor exposure (CIE). Seventy-two hours after CIE cessation, CIE and age-matched ethanol-naïve Air controls experienced auditory trace fear conditioning (TFC). Rats were tested for cue-mediated retrieval in the fear context either twenty-four hours (24 hr), ten days (10 days), or twenty-one days (21 days) later. CIE rats showed enhanced freezing behavior during TFC acquisition compared to Air rats. Air rats showed significant fear retrieval, and this behavior did not differ at the three time points. In CIE rats, fear retrieval increased over time during abstinence, indicating an incubation in fear responses. Enhanced retrieval at 21 days was associated with reduced structural and functional plasticity of ventral granule cell neurons (GCNs) and reduced expression of synaptic proteins important for neuronal plasticity. Systemic treatment with the drug Isoxazole-9 (Isx-9; small molecule that stimulates DG plasticity) during the last week and a half of CIE blocked altered acquisition and retrieval of fear memories in CIE rats during abstinence. Concurrently, Isx-9 modulated the structural and functional plasticity of ventral GCNs and the expression of synaptic proteins in the ventral DG. These findings identify that abstinence-induced disruption of fear memory consolidation occurs via altered plasticity within the ventral DG, and that Isx-9 prevented these effects.
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