The T-type calcium channel antagonist, Z944, alters social behavior in Genetic Absence Epilepsy Rats from Strasbourg.

Abstract

Abnormalities in social behavior are a co-morbid symptom of idiopathic generalized epilepsies such as childhood absence epilepsy. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model is a spontaneously occurring absence epilepsy phenotype closely correlated to that of human absence epilepsies. Similar to the human conditions, GAERS display social abnormalities. Previous studies have only demonstrated social abnormalities in female GAERS, whereas social problems are observed in male and female patients. Seizures in GAERS result in part due to a gain-of-function missense mutation in the Cav3.2 T-type calcium channel gene. This study examined the effects of the pan-T-type calcium channel antagonist, Z944, on social interaction behaviors in male and female GAERS using an open field social interaction test. A second objective of this study was to examine the effects of Z944 on anxiety-like behavior in an open field locomotion test and elevated plus maze. Results showed a decrease in social activity in GAERS relative to non-epileptic control (NEC) rats. Acute, systemic Z944 (5 mg/kg; i.p.) consistently reduced introductory and aggressive behaviors in both GAERS and NECs whereas strain effects were observed for over-and-under crawl behaviors. In the open field locomotion test and elevated plus maze, Z944 increased anxiety-like behaviors in GAERS, whereas, Z944 produced inconsistent effects on anxiety-like behaviors in NECs. The results of this study suggest that the regulation of T-type calcium channel activity may be a useful strategy for the development of new therapeutic approaches for the treatment of social and affective abnormalities observed in absence epilepsy disorders.

• Authors: Wendie N Marks, Nadine K Zabder, Stuart M Cain, Terrance P Snutch, John G Howland
• Journal: Behavioural brain research (Behav Brain Res) Vol. 361 Pg. 54-64 (04 01 2019) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 30550952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Channel Blockers
• Calcium Channels, T-Type
• Piperidines
• Z944

Topics

• Animals
• Anxiety (genetics)
• Behavior, Animal (drug effects)
• Brain (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, T-Type (drug effects)
• Disease Models, Animal
• Electroencephalography
• Epilepsy, Absence (genetics)
• Epilepsy, Generalized (genetics)
• Female
• Locomotion (drug effects)
• Male
• Piperidines (pharmacology)
• Rats
• Rats, Wistar
• Seizures (drug therapy)
• Social Behavior