Neurobiology of learning and memory
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Neurobiol Learn Mem · May 2013
Sodium butyrate-induced histone acetylation strengthens the expression of cocaine-associated contextual memory.
The conditioned place preference (CPP) paradigm entails Pavlovian conditioning and allows evaluating the acquisition and extinction of drug-associated memory. Epigenetic regulation of chromatin structure by acetylation and deacetylation of histone proteins is critical for formation of long-term memory (LTM). We have recently shown that a single administration of the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) facilitated extinction of fear-associated memory in mice. ⋯ Subjects that were conditioned by escalating schedule of cocaine and subsequently received repeated injections of NaB during daily reexposure to nonreinforced context showed either enhancement or no effect on place preference. Acute administration of NaB (1.2g/kg) to naïve mice resulted in marked increase in acetylation of histone H3 lysine 14 (H3K14) and histone H4 lysine 8 (H4K8) in hippocampus but not amygdala. Results suggest that regardless of the scheduling of either cocaine or NaB administration, NaB-induced histone hyperacetylation in the hippocampus may strengthen cocaine-associated contextual memory.
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Neurobiol Learn Mem · May 2013
Systemic administrations of β-estradiol alleviate both conditioned and sensitized fear responses in an ovariectomized rat model of post-traumatic stress disorder.
Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD. SPS rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced fear response to the traumatic cue (conditioned fear response) and hyper arousal (the sensitized fear response). In the present study we are looking at PTSD-like symptoms in rats. ⋯ Findings indicated that rats who received electric shock the day after SPS exhibited both enhanced conditioned and sensitized fear responses in comparison to the control group. β-estradiol in 45μg/kg dose could reduce both types of fear responses. β-estradiol exert an inhibitory influence on contextual fear conditioning (hippocampal-dependent) and on sensitized fear conditioning (amygdala-dependent). Single injection of this dose is enough for CFR alleviation but at least twice injections are necessary to reduce sensitized fear response. Overall our data demonstrate that multiple injections of β-estradiol, dose dependently, could alleviate both SPS induced conditioned and sensitized fear responses, as signs of PTSD.