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The impact of doxycycline on human contextual fear memory

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Bibliographic Details
Title: The impact of doxycycline on human contextual fear memory
Authors: Wehrli, Jelena M, Xia, Yanfang, Abivardi, Aslan, Kleim, Birgit, Bach, Dominik R
Contributors: University of Zurich, Bach, Dominik R
Source: Psychopharmacology (Berl)
Publication Status: Preprint
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: 0301 basic medicine, 10093 Institute of Psychology, Cognitive Neuroscience, MMP inhibition, Fear, HLC Healthy Longevity Center, Hippocampus, Memory modification, 03 medical and health sciences, 3004 Pharmacology, 0302 clinical medicine, Double-Blind Method, Memory, Doxycycline, Humans, Learning, Female, Double-Blind Method [MeSH], Female [MeSH], Humans [MeSH], Doxycycline/pharmacology [MeSH], Memory/physiology [MeSH], Memory consolidation, Hippocampus [MeSH], Fear memory, Original Investigation, Doxycycline/metabolism [MeSH], Learning/physiology [MeSH], Cues [MeSH], Fear/physiology [MeSH], Cues, 150 Psychology, Neuroscience
Description: Rationale Previous work identified an attenuating effect of the matrix metalloproteinase (MMP) inhibitor doxycycline on fear memory consolidation. This may present a new mechanistic approach for the prevention of trauma-related disorders. However, so far, this has only been unambiguously demonstrated in a cued delay fear conditioning paradigm, in which a simple geometric cue predicted a temporally overlapping aversive outcome. This form of learning is mainly amygdala dependent. Psychological trauma often involves the encoding of contextual cues, which putatively necessitates partly different neural circuits including the hippocampus. The role of MMP signalling in the underlying neural pathways in humans is unknown. Methods Here, we investigated the effect of doxycycline on configural fear conditioning in a double-blind placebo-controlled randomised trial with 100 (50 females) healthy human participants. Results Our results show that participants successfully learned and retained, after 1 week, the context-shock association in both groups. We find no group difference in fear memory retention in either of our pre-registered outcome measures, startle eye-blink responses and pupil dilation. Contrary to expectations, we identified elevated fear-potentiated startle in the doxycycline group early in the recall test, compared to the placebo group. Conclusion Our results suggest that doxycycline does not substantially attenuate contextual fear memory. This might limit its potential for clinical application.
Document Type: Article
Other literature type
File Description: ZORA_s00213_024_06540_w.pdf - application/pdf
Language: English
ISSN: 1432-2072
0033-3158
DOI: 10.1007/s00213-024-06540-w
DOI: 10.31234/osf.io/m5cyv
DOI: 10.5167/uzh-267659
Access URL: https://pubmed.ncbi.nlm.nih.gov/38334789
https://repository.publisso.de/resource/frl:6497570
Rights: CC BY
Accession Number: edsair.doi.dedup.....b72174809301ace4dae4f9760f50cb51
Database: OpenAIRE
Description
Abstract:Rationale Previous work identified an attenuating effect of the matrix metalloproteinase (MMP) inhibitor doxycycline on fear memory consolidation. This may present a new mechanistic approach for the prevention of trauma-related disorders. However, so far, this has only been unambiguously demonstrated in a cued delay fear conditioning paradigm, in which a simple geometric cue predicted a temporally overlapping aversive outcome. This form of learning is mainly amygdala dependent. Psychological trauma often involves the encoding of contextual cues, which putatively necessitates partly different neural circuits including the hippocampus. The role of MMP signalling in the underlying neural pathways in humans is unknown. Methods Here, we investigated the effect of doxycycline on configural fear conditioning in a double-blind placebo-controlled randomised trial with 100 (50 females) healthy human participants. Results Our results show that participants successfully learned and retained, after 1 week, the context-shock association in both groups. We find no group difference in fear memory retention in either of our pre-registered outcome measures, startle eye-blink responses and pupil dilation. Contrary to expectations, we identified elevated fear-potentiated startle in the doxycycline group early in the recall test, compared to the placebo group. Conclusion Our results suggest that doxycycline does not substantially attenuate contextual fear memory. This might limit its potential for clinical application.
ISSN:14322072
00333158
DOI:10.1007/s00213-024-06540-w