Infusion of cannabidiol into infralimbic cortex facilitates fear extinction via CB1 receptors

•Intra-IL infusion of cannabidiol facilitates extinction of contextual fear.•Rimonabant blocks the facilitating effect of intra-IL cannabidiol on fear extinction.•Cannabidiol may have a therapeutical potential in fear regulation in humans. Previous studies have implicated cannabinoids in extinction...

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Bibliographic Details
Published in:Behavioural brain research 2013-08, Vol.250, p.23-27
Main Authors: Do Monte, Fabricio H., Souza, Rimenez R., Bitencourt, Rafael M., Kroon, Juliana A., Takahashi, Reinaldo N.
Format: Article
Language:English
Subjects:
Animals
Behavioral psychophysiology
Biological and medical sciences
Cannabidiol
Cannabidiol - pharmacology
Cannabinoid Receptor Antagonists - pharmacology
CB1 receptor
Cerebral Cortex - drug effects
Cerebral Cortex - physiology
Conditioned freezing
Conditioning, Classical - drug effects
Dose-Response Relationship, Drug
Drug Interactions
Electroshock - adverse effects
Extinction, Psychological - drug effects
Fear - drug effects
Fear - psychology
Fear extinction
Freezing Reaction, Cataleptic - drug effects
Fundamental and applied biological sciences. Psychology
Infralimbic cortex
Male
Microinjections
Piperidines - pharmacology
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Pyrazoles - pharmacology
Rats
Rats, Long-Evans
Receptor, Cannabinoid, CB1 - metabolism
Rimonabant
Time Factors
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Summary:•Intra-IL infusion of cannabidiol facilitates extinction of contextual fear.•Rimonabant blocks the facilitating effect of intra-IL cannabidiol on fear extinction.•Cannabidiol may have a therapeutical potential in fear regulation in humans. Previous studies have implicated cannabinoids in extinction of conditioned fear. We have recently showed that intraventricular infusion of the phytocannabinoid cannabidiol (CBD) facilitates fear extinction, but the brain regions underlying this effect remained unknown. Here we demonstrate that repeated microinjections of CBD into the infralimbic cortex (IL) facilitated fear extinction, as indicated by reduced levels of freezing during extinction test. Systemic administration of the CB1 receptor antagonist rimonabant blocked the effects of intra-IL CBD, suggesting that CBD acts through CB1 receptors to facilitate fear extinction. Our findings suggest a potential therapeutic use of CBD for extinction-based therapies of aversive memories in humans.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2013.04.045