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Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: reduced dopaminergic modulation and immediate gene expression in limbic circuits
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, Repositório Institucional da UFRN, Universidade Federal do Rio Grande do Norte (UFRN), instacron:UFRN
- Publication Year :
- 2017
-
Abstract
- The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of posttraumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5 h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5 h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5 days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits.
- Subjects :
- Male
0301 basic medicine
Time Factors
Thalamus
Gene Expression
Prefrontal Cortex
Hippocampus
Amygdala
Stress Disorders, Post-Traumatic
03 medical and health sciences
cannabidiol
0302 clinical medicine
Neurochemical
Conditioning, Psychological
medicine
Animals
Cannabidiol
Rats, Wistar
Prefrontal cortex
NEUROTRANSMISSORES
Memory Consolidation
Neurons
contextual fear memory
C-fos
General Neuroscience
Fear
030104 developmental biology
medicine.anatomical_structure
nervous system
NMDA receptor
Memory consolidation
dopamine
Psychology
Neuroscience
030217 neurology & neurosurgery
medial prefrontal cortex
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, Repositório Institucional da UFRN, Universidade Federal do Rio Grande do Norte (UFRN), instacron:UFRN
- Accession number :
- edsair.doi.dedup.....da1730ddb75d642ff97cb42e7470fdfd