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

• Published in: Pharmacology Vol. 105; no. 9-10; p. 561
• Main Authors: Yananli, Hasan Raci, Demirkapu, Mahluga Jafarova, Sakallı, Halil Eren, Gülhan, Rezzan, Onat, Filiz Yılmaz
• Format: Journal Article
• Language: English
• Published: Switzerland 2020
• Subjects: Animals; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - drug effects; Calcium Channels, T-Type - metabolism; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy, Absence - drug therapy; Epilepsy, Absence - genetics; Epilepsy, Absence - physiopathology; Female; Infusions, Intraventricular; Injections, Intraperitoneal; Male; Piperazines - administration & dosage; Piperazines - pharmacology; Rats; Rats, Wistar; Somatosensory Cortex - drug effects; Somatosensory Cortex - physiopathology; Tropolone - administration & dosage; Tropolone - analogs & derivatives; Tropolone - pharmacology; Rats; Calcium channel blocker; Epilepsy; Cortex; Spike-and-wave discharges
• DOI: 10.1159/000505215

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