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Selective Blockade of T-Type Ca2+ Channels is Protective Against Alcohol-Withdrawal Induced Seizure and Mortality.

Authors :
Masicampo, Melissa L
Shan, Hong Qu
Xu, Victoria
Speagle, Merritt
Godwin, Dwayne W
Source :
Alcohol & Alcoholism; Sep2018, Vol. 53 Issue 5, p526-531, 6p
Publication Year :
2018

Abstract

Aims We have previously demonstrated that blockade of T-type calcium channels by the non-selective antagonist, ethosuximide (ETX), is effective at reducing electrographical and behavioral correlates of alcohol-withdrawal (WD) seizure. Here, we investigated whether blockade of these calcium channels with the selective antagonist TTA-P2 also reduces alcohol-WD seizure. Short summary The non-specific T-type calcium channel antagonist, ETX, is protective against alcohol-WD seizure. However, the mechanism of this effect is unclear. Here, we provide evidence that further suggests selective blockade of T-type calcium channels are protective against alcohol-WD seizure and WD-related mortality. Methods We used an intermittent ethanol exposure model to produce WD-induced hyperexcitability in DBA/2 J mice. Seizure severity was intensified with the chemoconvulsant pentylenetetrazole (PTZ). Results TTA-P2 (10 mg/kg) reduced seizure severity in mice undergoing alcohol WD with concurrent PTZ treatment (20 mg/kg). Moreover, TTA-P2 (20 and 40 mg/kg) was also protective against PTZ-induced (40 mg/kg) seizure and mortality. Conclusions These results are consistent with prior results using ETX, and suggest that the protective effects of ETX and TTA-P2 against EtOH WD seizures are mediated by T-type calcium channels. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
07350414
Volume :
53
Issue :
5
Database :
Complementary Index
Journal :
Alcohol & Alcoholism
Publication Type :
Academic Journal
Accession number :
131384442
Full Text :
https://doi.org/10.1093/alcalc/agy042