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Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches.

ABSTRACT: The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission; the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT1ARs), and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1AR, GABAARs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABAARs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htr1a, Grin2a, Gabra5, and Erk2 after the retention test and of Htr1a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT1ARs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htr1a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments.

SUBMITTER: de Oliveira DR

PROVIDER: S-EPMC4700274 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches.

de Oliveira Daniela R DR Zamberlam Claudia R CR Rêgo Gizelda M GM Cavalheiro Alberto A Cerutti Janete M JM Cerutti Suzete M SM

Frontiers in behavioral neuroscience 20160105

The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission; the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT1ARs), and the gamma-aminobutyric acid type A receptors (GABAARs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to condition ...[more]

PMID: 26778988

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Project description:Recently, the dynamic properties of brain activity rather than its stationary values have attracted more interest in clinical applications. It has been shown that brain signals exhibit scale-free dynamics or long-range temporal correlations (LRTC) that differ between rest and cognitive tasks in healthy controls and clinical groups. Little is known about how fear-inducing tasks may influence dispersion and the LRTC of subsequent resting-state brain activity. In this study, we aimed to explore the changes in the variance and scale-free properties of the brain's blood oxygenation level-dependent (BOLD) signal during the resting-state sessions before and after fear learning and fear memory extinction. During a 1-h break between magnetic resonance imaging (MRI) scanning, 23 healthy, right-handed volunteers experienced a fear extinction procedure, followed by Pavlovian fear conditioning that included partial reinforcement using mild electrical stimulation. We extracted the average time course of the BOLD signal from 245 regions of interest (ROIs) taken from the resting-state functional atlas. The variance of the BOLD signal and the Hurst exponent (H), which reflects the scale-free dynamic, were compared in the resting states before and after fear learning and fear memory extinction. After fear extinction, six ROIs showed a difference in H at the uncorrected level of significance, including areas associated with fear processing. H decreased during fear extinction but then became higher than before fear learning, specifically in areas related to the fear extinction network (FEN). However, activity in the other ROIs restored the H to its initial level. The variance of the BOLD signal in six ROIs demonstrated a significant increase from initial rest to the post-task rest. A limited number of ROIs showed changes in both H and variance. Our results imply that the variability and scale-free properties of the BOLD signal might serve as additional indicators of changes in spontaneous brain activity related to recent experience.

Dataset Information

Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches.

Publications

Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches.

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