Serotonergic Modulation of Conditioned Fear

Judith R Homberg

doi:10.6064/2012/821549

Abstract

Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall), is essential in the understanding of (individual differences in vulnerability to) these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI) treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

Highlights

Persistence of conditioned fear is a core process in the development of posttraumatic stress disorder (PTSD) as well as other anxiety-related disorders and depression [1]
5-HT plays an essential role in conditioned fear, but do the studies reviewed here provide a general view on the precise nature of 5-HT’s role? e insights that the studies provide are as follows
(b) Acute selective serotonin reuptake inhibitor (SSRI) treatment reduces the expression of contextual fear and increases the expression of cued fear

Summary

Introduction

Persistence of conditioned fear is a core process in the development of posttraumatic stress disorder (PTSD) as well as other anxiety-related disorders and depression [1]. An issue that is occupying scientists for decades is the phenomenon that some individuals more than others are vulnerable to engage into increased conditioned fear responses. It is my aim to highlight the role of serotonin in conditioned fear. Serotonin (5-HT) is an ancient molecule that may help the individual to attune behaviour towards speci c elements of the environment, conditioned stimuli. As understanding of the conditioning processes affected by 5-HT is extremely useful in, for example, the timing of antidepressant or anxiolytic treatment and the development of individualized behavioural cognitive therapies, it is my aim to provide an overview of human and rodent fear conditioning studies manipulating the serotonergic system in various ways and to propose new views on the speci c function of 5-HT. I used PubMed as tool to search literature and employed the key words “serotonin” and “fear conditioning.”

Behavioural Measures of Conditioned Fear

The Neural Circuits Underlying

The Serotonergic System

Selective Serotonin Reuptake Inhibitors

Serotonin Depletion

Discussion and Conclusions