Fluoxetine acts concomitantly on dorsal and ventral hippocampus to Trk-dependently modulate the extinction of fear memory

ABSTRACTBackgroundHippocampus can be divided along its longitudinal axis into dorsal and ventral parts. Both are usually committed to modulate different aspects of behavior and stress response. However, it is not clear whether the hippocampal subregions could differently modulate the effect of antidepressant drugs. Since fluoxetine (FLX) effect on extinction of aversive memory is well known to depend on hippocampal BDNF levels, we hypothesized that the hippocampal subregions might play different roles in fluoxetine efficacy in decreasing fear response.MethodWistar rats were fear-cued conditioned and treated chronically with fluoxetine to enhance their subsequent extinction memory. First, FLX effect on BDNF levels was assessed considering the dorsal (dHC) and ventral (vHC) hippocampus apart. Then, K252a (a functional Trk blocker) was infused either into the dHC or vHC to assay its interaction with FLX treatment over the fear response. Next, BDNF was directly infused into either the dHC or vHC to compare its behavioral effects with FLX. Finally, FLX effect on c-Fos expression was evaluated also considering the dHC and vHC apart, along with subareas of amygdala and medial prefrontal cortex.ResultsChronic FLX treatment increased BDNF in the dHC, whereas BDNF was increased in the vHC after acute treatment only. K252a infused after the extinction protocol into either dHC or vHC was able to prevent FLX effect on fear response. BDNF directly infused into the dHC increased fear response, however its administration into the vHC induced an opposite effect. Besides, a negative correlation between the fear response and c-Fos expression was observed after chronic FLX treatment specifically in the dHC CA3/CA1 and vHC CA1/DG.ConclusionBoth dHC and vHC are important for the Trk-dependent FLX effect on extinction memory, although a discrepancy on the fear response was observed with the direct infusion of BDNF into the dHC or vHC.

Download Full-text

Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis

FOCUS The Journal of Lifelong Learning in Psychiatry ◽

10.1176/appi.focus.16407 ◽

2018 ◽

Vol 16 (4) ◽

pp. 420-429 ◽

Cited By ~ 20

Author(s):

Andrea Cipriani ◽

Toshi A Furukawa ◽

Georgia Salanti ◽

Anna Chaimani ◽

Lauren Z Atkinson ◽

...

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Acute Treatment ◽

Meta Analysis ◽

Antidepressant Drugs ◽

Comparative Efficacy ◽

Major Depressive

Download Full-text

Fear memory retrieval induces CREB phosphorylation and Fos expression within the amygdala

European Journal of Neuroscience ◽

10.1046/j.0953-816x.2001.01531.x ◽

2001 ◽

Vol 13 (7) ◽

pp. 1453-1458 ◽

Cited By ~ 125

Author(s):

Jeremy Hall ◽

Kerrie L. Thomas ◽

Barry J. Everitt

Keyword(s):

Memory Retrieval ◽

Fear Memory ◽

Creb Phosphorylation ◽

Fos Expression

Download Full-text

Genotoxic and mutagenic effects of vigabatrin, a γ-aminobutyric acid transaminase inhibitor, in Wistar rats submitted to rotarod task

Human & Experimental Toxicology ◽

10.1177/0960327115611970 ◽

2016 ◽

Vol 35 (9) ◽

pp. 958-965 ◽

Cited By ~ 5

Author(s):

VR Coelho ◽

K Sousa ◽

TR Pires ◽

DKM Papke ◽

CG Vieira ◽

...

Keyword(s):

Acute Treatment ◽

Wistar Rats ◽

Micronucleus Test ◽

Repeated Administration ◽

Saline Group ◽

Aminobutyric Acid ◽

Subchronic Treatment ◽

Motor Activities ◽

Male Wistar Rats ◽

Mutagenic Effects

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.

Download Full-text

Long-Lasting Reductions of Ethanol Drinking, Enhanced Ethanol-Induced Sedation, and Decreased c-fos Expression in the Edinger-Westphal Nucleus in Wistar Rats Exposed to the Organophosphate Chlorpyrifos

Toxicological Sciences ◽

10.1093/toxsci/kfl194 ◽

2006 ◽

Vol 96 (2) ◽

pp. 310-320 ◽

Cited By ~ 4

Author(s):

F. Carvajal ◽

M. Lopez-Grancha ◽

M. Navarro ◽

M. d. C. Sanchez-Amate ◽

I. Cubero

Keyword(s):

Wistar Rats ◽

Ethanol Drinking ◽

Fos Expression ◽

Edinger Westphal Nucleus

Download Full-text

Propranolol-induced inhibition of unconditioned stimulus-reactivated fear memory prevents the return of fear in humans

Translational Psychiatry ◽

10.1038/s41398-020-01023-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jiahui Deng ◽

Le Shi ◽

Kai Yuan ◽

Ping Yao ◽

Sijing Chen ◽

...

Keyword(s):

Unconditioned Stimulus ◽

Memory Retrieval ◽

Adrenergic Receptor ◽

Fear Memory ◽

Fear Response ◽

Return Of Fear ◽

The Us ◽

Propranolol Administration ◽

Retrieval Interference ◽

Oral Propranolol

Abstract Fear memories can be reactivated by a fear-associated conditioned stimulus (CS) or unconditioned stimulus (US) and then undergo reconsolidation. Propranolol administration during CS retrieval-induced reconsolidation can impair fear memory that is specific to the reactivated CS. However, from a practical perspective, the US is often associated with multiple CSs, and each CS can induce a fear response. The present study sought to develop and test a US-based memory retrieval interference procedure with propranolol to disrupt the original fear memory and eliminate all CS-associated fear responses in humans. We recruited 127 young healthy volunteers and conducted three experiments. All of the subjects acquired fear conditioning, after which they received the β-adrenergic receptor antagonist propranolol (40 mg) or placebo (vitamin C) and were exposed to the US or CS to reactivate the original fear memory. Fear responses were measured. Oral propranolol administration 1 h before US retrieval significantly decreased subsequent fear responses and disrupted associations between all CSs and the US. However, propranolol administration before CS retrieval only inhibited the fear memory that was related to the reactivated CS. Moreover, the propranolol-induced inhibition of fear memory reconsolidation that was retrieved by the US had a relatively long-lasting effect (at least 2 weeks) and was also effective for remote fear memory. These findings indicate that the US-based memory retrieval interference procedure with propranolol can permanently decrease the fear response and prevent the return of fear for all CSs in humans. This procedure may open new avenues for treating fear-related disorders.

Download Full-text

Avoidance Behavior Prevents Modification of Fear Memory During Reconsolidation

Psychological Reports ◽

10.1177/0033294118811116 ◽

2018 ◽

Vol 123 (2) ◽

pp. 224-238 ◽

Cited By ~ 2

Author(s):

Yusuke Nitta ◽

Toru Takahashi ◽

Tomosumi Haitani ◽

Eriko Sugimori ◽

Hiroaki Kumano

Keyword(s):

Conditioned Stimulus ◽

Avoidance Behavior ◽

Spontaneous Recovery ◽

Safety Information ◽

Fear Memory ◽

Extinction Training ◽

Relevant Factor ◽

Fear Response ◽

New Information

Several studies have revealed that fear recovery is prevented when extinction training is conducted after retrieval of a fear memory. Postretrieval extinction training is related to modification of memory during reconsolidation. Providing new information during reconsolidation can modify the original memory. We propose that avoidance behavior is a relevant factor that prevents subjects from obtaining new safety information during reconsolidation. Postretrieval extinction training without avoidance behavior reduced the fear response to conditioned stimulus and prevented spontaneous recovery in the current study, which corresponded with previous studies. Under the condition of postretrieval extinction training with avoidance behavior, the fear response was not reduced as much as it was in the condition without avoidance. It is possible that avoidance behavior prevents receiving new safety information during postretrieval extinction training.

Download Full-text