The T-type calcium channel blocker Z944 reduces conditioned fear in Genetic Absence Epilepsy Rats from Strasbourg and the non-epileptic control strain.
Animals
Calcium Channel Blockers
/ pharmacology
Calcium Channels, T-Type
/ genetics
Conditioning, Classical
/ drug effects
Disease Models, Animal
Epilepsy, Absence
/ genetics
Extinction, Psychological
/ drug effects
Fear
/ drug effects
Female
Male
Memory
/ drug effects
Piperidines
/ pharmacology
Rats
acquisition
extinction
learning
memory
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
03
10
2018
revised:
01
03
2019
accepted:
08
03
2019
pubmed:
20
3
2019
medline:
13
8
2020
entrez:
20
3
2019
Statut:
ppublish
Résumé
Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are a rodent model of childhood absence epilepsy (CAE) that display a gain-of-function mutation in the gene encoding the Cav3.2 T-type calcium channel. GAERS demonstrate heightened learning and delayed extinction of fear conditioning. Our objective in the present study was to examine the effects of the pan-T-type calcium channel blocker Z944 on the acquisition, consolidation and extinction of conditioned fear in GAERS and the non-epileptic control (NEC) strain. Z944 (10 mg/kg; ip) was administered 15 min prior to either acquisition, extinction day 1 (24 hr later), acquisition and extinction day 1, or during the consolidation (post-acquisition) of tone-cued fear conditioning. Extinction was examined 24 and 48 hr after conditioning. In drug naïve GAERS, increased freezing during the acquisition and extinction phases of fear conditioning was found. Short-term effects of Z944 on performance were observed as Z944 increased freezing during testing on the day it was administered. Z944 administered prior to the acquisition phase had a long-term effect on extinction. Specifically, both GAERS and NECs showed a decrease in freezing during extinction relative to drug naïve GAERS and NEC rats respectively. Regardless of strain or treatment, female rats showed reduced extinction of fear relative to male rats. These results demonstrate that T-type calcium channels contribute to the neural systems that mediate the learning and memory of conditioned fear. Overall, these findings suggest that T-type calcium channel blockers show promise in the treatment of learning impairments observed in disorders such as CAE.
Substances chimiques
Calcium Channel Blockers
0
Calcium Channels, T-Type
0
Piperidines
0
Z944
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3046-3059Subventions
Organisme : CIHR
ID : 10677
Pays : Canada
Organisme : CIHR
ID : 125984
Pays : Canada
Informations de copyright
© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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