Cargando…

Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction

Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.p. injections...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Chenchen, Stevenson, Carl W., Guimaraes, Francisco S., Lee, Jonathan L. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159417/
https://www.ncbi.nlm.nih.gov/pubmed/28018227
http://dx.doi.org/10.3389/fphar.2016.00493
_version_ 1782481766660964352
author Song, Chenchen
Stevenson, Carl W.
Guimaraes, Francisco S.
Lee, Jonathan L. C.
author_facet Song, Chenchen
Stevenson, Carl W.
Guimaraes, Francisco S.
Lee, Jonathan L. C.
author_sort Song, Chenchen
collection PubMed
description Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.p. injections of cannabidiol (10 mg/kg) with those of the NMDA receptor antagonist MK-801 (0.1 mg/kg) and partial agonist D-cycloserine (DCS; 15 mg/kg) in order to determine the mnemonic basis of long-term fear reduction. We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test. The latter test reduction was replicated by DCS, but MK-801 instead elevated test freezing. In contrast, when initial conditioning was weaker, CBD and MK-801 had similar effects to increase freezing at the fear retention test relative to vehicle controls, whereas DCS had no observable impact. This pattern of results is consistent with CBD enhancing contextual fear memory extinction when the initial conditioning is strong, but impairing extinction when conditioning is weak. This bidirectional effect of CBD may be related to stress levels induced by conditioning and evoked at retrieval during extinction, rather than the strength of the memory per se.
format Online
Article
Text
id pubmed-5159417
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-51594172016-12-23 Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction Song, Chenchen Stevenson, Carl W. Guimaraes, Francisco S. Lee, Jonathan L. C. Front Pharmacol Pharmacology Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.p. injections of cannabidiol (10 mg/kg) with those of the NMDA receptor antagonist MK-801 (0.1 mg/kg) and partial agonist D-cycloserine (DCS; 15 mg/kg) in order to determine the mnemonic basis of long-term fear reduction. We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test. The latter test reduction was replicated by DCS, but MK-801 instead elevated test freezing. In contrast, when initial conditioning was weaker, CBD and MK-801 had similar effects to increase freezing at the fear retention test relative to vehicle controls, whereas DCS had no observable impact. This pattern of results is consistent with CBD enhancing contextual fear memory extinction when the initial conditioning is strong, but impairing extinction when conditioning is weak. This bidirectional effect of CBD may be related to stress levels induced by conditioning and evoked at retrieval during extinction, rather than the strength of the memory per se. Frontiers Media S.A. 2016-12-16 /pmc/articles/PMC5159417/ /pubmed/28018227 http://dx.doi.org/10.3389/fphar.2016.00493 Text en Copyright © 2016 Song, Stevenson, Guimaraes and Lee. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Song, Chenchen
Stevenson, Carl W.
Guimaraes, Francisco S.
Lee, Jonathan L. C.
Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title_full Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title_fullStr Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title_full_unstemmed Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title_short Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
title_sort bidirectional effects of cannabidiol on contextual fear memory extinction
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159417/
https://www.ncbi.nlm.nih.gov/pubmed/28018227
http://dx.doi.org/10.3389/fphar.2016.00493
work_keys_str_mv AT songchenchen bidirectionaleffectsofcannabidioloncontextualfearmemoryextinction
AT stevensoncarlw bidirectionaleffectsofcannabidioloncontextualfearmemoryextinction
AT guimaraesfranciscos bidirectionaleffectsofcannabidioloncontextualfearmemoryextinction
AT leejonathanlc bidirectionaleffectsofcannabidioloncontextualfearmemoryextinction