Journal article
Opposing effects of D-cycloserine on fear despite a common extinction duration: interactions between brain regions and behavior
Neurobiology of learning and memory, Vol.113, pp.25-34
09/01/2014
DOI: 10.1016/j.nlm.2013.12.009
PMCID: PMC4053504
PMID: 24374132
Abstract
A number of studies have reported that D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate glutamate receptor, can facilitate the loss of conditioned fear if it is administered during an extinction trial. Here we examine the effects of DCS injected into the hippocampus or amygdala on extinction of context-evoked freezing after contextual fear conditioning in C57BL/6 mice. We find that DCS administered prior to an extinction session decreased freezing from the outset of the session regardless of which brain region was targeted. Retention tests revealed opposite effects on fear expression despite identical behavioral treatments: intra-hippocampal DCS inhibited fear expression while intra-amygdala DCS potentiated fear expression. Following post-extinction session injections of DCS, we found a similar though less pronounced effect. Closer inspection of the data revealed that the effects of DCS interacted with the behavior of the subjects during extinction. Intra-hippocampal injections of DCS enhanced extinction in those mice that showed the greatest amount of within-session extinction, but had less pronounced effects on mice that showed the least within-session extinction. Intra-amygdala injections of DCS impaired extinction in those mice that showed the least within-session extinction, but there was some evidence that the effect in the amygdala did not depend on behavior during extinction. These findings demonstrate that even with identical extinction trial durations, the effects of DCS administered into the hippocampus and amygdala can heavily depend on the organism's behavior during the extinction session. The broader implication of these findings is that the effects of pharmacological treatments designed to enhance extinction by targeting hippocampal or amygdalar processes may depend on the responsivity of the subject to the behavioral treatment.
Details
- Title: Subtitle
- Opposing effects of D-cycloserine on fear despite a common extinction duration: interactions between brain regions and behavior
- Creators
- Scott S Bolkan - Oregon Health & Science UniversityK Matthew Lattal - Oregon Health & Science University
- Resource Type
- Journal article
- Publication Details
- Neurobiology of learning and memory, Vol.113, pp.25-34
- DOI
- 10.1016/j.nlm.2013.12.009
- PMID
- 24374132
- PMCID
- PMC4053504
- NLM abbreviation
- Neurobiol Learn Mem
- ISSN
- 1074-7427
- eISSN
- 1095-9564
- Grant note
- R01 MH077111 / NIMH NIH HHS MH077111 / NIMH NIH HHS R01 DA025922 / NIDA NIH HHS
- Language
- English
- Date published
- 09/01/2014
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984945143102771
Metrics
4 Record Views