Anandamide Signaling Augmentation Rescues Amygdala Synaptic Function and Comorbid Emotional Alterations in a Model of Epilepsy.
Affective Symptoms
/ etiology
Amidohydrolases
/ physiology
Amygdala
/ physiopathology
Animals
Anxiety
/ psychology
Arachidonic Acids
Endocannabinoids
Epilepsy
/ complications
Fear
/ psychology
Glutamic Acid
/ physiology
Kindling, Neurologic
Male
Polyunsaturated Alkamides
Rats
Rats, Long-Evans
Signal Transduction
Synapses
gamma-Aminobutyric Acid
/ physiology
FAAH
amygdala
anandamide
emotional behavior
epilepsy
synaptic plasticity
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
ISSN: 1529-2401
Titre abrégé: J Neurosci
Pays: United States
ID NLM: 8102140
Informations de publication
Date de publication:
29 07 2020
29 07 2020
Historique:
received:
09
01
2020
revised:
14
05
2020
accepted:
21
06
2020
pubmed:
1
7
2020
medline:
1
1
2021
entrez:
1
7
2020
Statut:
ppublish
Résumé
Epilepsy is often associated with emotional disturbances and the endocannabinoid (eCB) system tunes synaptic transmission in brain regions regulating emotional behavior. Thus, persistent alteration of eCB signaling after repeated seizures may contribute to the development of epilepsy-related emotional disorders. Here we report that repeatedly eliciting seizures (kindling) in the amygdala caused a long-term increase in anxiety and impaired fear memory retention, which was paralleled by an imbalance in GABA/glutamate presynaptic activity and alteration of synaptic plasticity in the basolateral amygdala (BLA), in male rats. Anandamide (AEA) content was downregulated after repeated seizures, and pharmacological enhancement of AEA signaling rescued seizure-induced anxiety by restoring the tonic control of the eCB signaling over glutamatergic transmission. Moreover, AEA signaling augmentation also rescued the seizure-induced alterations of fear memory by restoring the phasic control of eCB signaling over GABAergic activity and plasticity in the BLA. These results indicate that modulation of AEA signaling represents a potential and promising target for the treatment of comorbid emotional dysfunction associated with epilepsy.
Identifiants
pubmed: 32601243
pii: JNEUROSCI.0068-20.2020
doi: 10.1523/JNEUROSCI.0068-20.2020
pmc: PMC7392500
doi:
Substances chimiques
Arachidonic Acids
0
Endocannabinoids
0
Polyunsaturated Alkamides
0
Glutamic Acid
3KX376GY7L
gamma-Aminobutyric Acid
56-12-2
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
anandamide
UR5G69TJKH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6068-6081Subventions
Organisme : CIHR
ID : PJT-162204
Pays : Canada
Organisme : CIHR
ID : FRN-162177
Pays : Canada
Organisme : CIHR
ID : PJT-159454
Pays : Canada
Informations de copyright
Copyright © 2020 the authors.
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