Effect of U-92032, T-Type Ca2+ Channel Blocker, on Rats with Genetic Absence Epilepsy.

Abstract

INTRODUCTION:

Absence epilepsy is associated with diffuse spike-and-wave discharges (SWD) on the electroencephalogram (EEG). Recent studies have demonstrated that the primary somatosensory cortex is also implicated in the generation of the SWDs.

OBJECTIVE:

This study investigated the effects of systemic and local administrations of U-92032 into the brain of Genetic Absence Epilepsy Rats from Strasbourg (GAERS).

METHODS:

GAERS animals underwent stereotaxic surgery for the placement of EEG recording electrodes and guide cannulas for U-92032 administration into the lateral ventricle (intracerebroventricular [i.c.v.]), upper lips area (S1Ulp) or barrel field area (S1B) of primary somatosensory cortex. Following 7 days of recovery, electrical activity was recorded continuously for 1 h before and 6 h after intraperitoneal (0.25; 1; 5 mg/kg i.p.) or local U-92032 or dimethyl sulfoxide (DMSO) injections.

RESULTS:

No changes were detected in the cumulative duration, mean duration, and number of SWDs following i.p. U-92032 injections. Local i.c.v. injections of U-92032 caused a significant decrease in the cumulative duration (i.c.v., 50 and 100 nmol/L), mean duration (i.c.v., 50, 100, and 250 nmol/L), and the number (i.c.v., 250 nmol/L) of SWDs compared to DMSO groups. Intra-cortical (S1Ulp and S1B) U-92032 injections caused a significant decrease in all 3 parameters compared to DMSO groups, as well.

CONCLUSION:

Intra-cortical injection of U-92032 caused almost complete removal of SWDs in GAERS and i.c.v. administration resulted in a significant reduction. However, systemic i.p. administration did not cause a significant change with the applied -doses.

• Authors: Hasan Raci Yananli, Mahluga Jafarova Demirkapu, Halil Eren Sakallı, Rezzan Gülhan, Filiz Yılmaz Onat
• Journal: Pharmacology (Pharmacology) Vol. 105 Issue 9-10 Pg. 561-567 ( 2020) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 32101873 (Publication Type: Journal Article)
• Copyright: © 2020 S. Karger AG, Basel.

Chemical References

• Calcium Channel Blockers
• Calcium Channels, T-Type
• Piperazines
• U 92032
• Tropolone

Topics

• Animals
• Calcium Channel Blockers (administration & dosage, pharmacology)
• Calcium Channels, T-Type (drug effects, metabolism)
• Disease Models, Animal
• Electrodes, Implanted
• Electroencephalography
• Epilepsy, Absence (drug therapy, genetics, physiopathology)
• Female
• Infusions, Intraventricular
• Injections, Intraperitoneal
• Male
• Piperazines (administration & dosage, pharmacology)
• Rats
• Rats, Wistar
• Somatosensory Cortex (drug effects, physiopathology)
• Tropolone (administration & dosage, analogs & derivatives, pharmacology)