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Serotonergic and dopaminergic modulation of the prevention of return of fear using reconsolidation.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Sektionen för farmakologi, Göteborgs universitet.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Disruption of fear reconsolidation results in permanent memory suppression in fear conditioning protocols in animals and humans. Serotonergic and dopaminergic polymorphisms have been associated to this process. Specifically, reacquisition of fear after disrupted reconsolidation was compromised in human short alle carriers of the serotonin transporter gene linked polymorphic region (5-HTTLPR) and in val/val homozygotes of the val158met catechol-O-methyltransferease (COMT) functional polymorphisms. The present study examined if the gene effects similarly would impact reinstatement, another measure reflecting return of fear, following unpaired shock presentations. Skin conductance responses served as the measure of acquisition, extinction and return of fear. During the reinstatement session return of fear tended to be stronger in in val/val homozygotes of the COMT polymorphism who extinguished outside (6 h) as compared to inside (10 min) the reconsolidation interval following a memory reminder. Carriers of the short allele of the 5-HTTLPR polymorphism displayed a similar pattern in response to the previously shock associated cue. These results partially replicate for reinstatement the gene effect demonstrated previously for reacquisition, but fail to conceptually replicate the main effect averaged over all genotypes. Collectively, data support that reconsolidation of human fear memory is influenced by dopaminergic and serotonergic genes.

Keyword [en]
Memory reconsolidation; fear conditioning; cold pressor test; serotonin; dopamine; polymorphism; genes
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-180200OAI: oai:DiVA.org:uu-180200DiVA: diva2:548751
Funder
Swedish Research CouncilFAS, Swedish Council for Working Life and Social Research
Available from: 2012-08-31 Created: 2012-08-31 Last updated: 2013-01-23
In thesis
1. Erasing Fear: Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity
Open this publication in new window or tab >>Erasing Fear: Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fear memories, here defined as learned associations between a stimulus and a physiological fear reaction, are formed through fear conditioning. In animals, fear memories, present in the lateral amygdala, undergo reconsolidation after recall. Moreover, this reconsolidation process can be disrupted both pharmacologically and behaviourally, resulting in a reduced fear response to the stimulus. This thesis examines the attenuation of fear memories by disrupting reconsolidation in humans, using measures of both the central and peripheral nervous system activity. Serotonergic and dopaminergic genes have previously been tied to both fear conditioning and anxiety disorders, where fear conditioning mechanisms are important. In order to evaluate the possible role of fear memory reconsolidation mechanims in the effect on fear and anxiety by these genes, this thesis also compare the reconsolidation disruption effect between different serotonergic and dopaminergic genotypes.

Study I examined the attentuation of fear memories by disrupting reconsolidation in humans using reacquisition as a measure of the return of fear. Moreover, study I investigated the impact of differences in serotonergic and dopaminergic alleles on this process.

Study II examined the attentuation of fear memories by disrupting reconsolidation in humans using reinstatement as a measure of the return of fear. Study II also investigated the impact of differences in serotonergic and dopaminergic alleles on the process of fear memory reconsolidation.

Study III used psychophysiology and fMRI to localize the functional neural activity mediating the fear memory reconsolidation disruption effect.

In summary, this thesis provides evidence that fear memories are attenuated by reconsolidation disruption in humans and that serotonergic and dopaminergic alleles influence this process. Moreover, this thesis support that human fear memory reconsolidation is amygdala-dependent, suggesting an evolutionary shared memory mechanism.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 81
Keyword
Memory reconsolidation; fear conditioning; serotonin; dopamine; polymorphism; gene; exposure therapy; fMRI; amygdala
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-180202 (URN)978-91-554-8455-2 (ISBN)
Public defence
2012-10-12, Universitetshuset, Sal IX, Biskopsgatan 3, Uppsala, 13:15 (Swedish)
Supervisors
Funder
Swedish Research Council
Available from: 2012-09-21 Created: 2012-08-31 Last updated: 2013-01-23Bibliographically approved

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